Pharmaceutical glass coating for achieving particle reduction

ABSTRACT

Embodiments of the present disclosure are directed to coated glass articles which reduce glass particle formation caused by glass to glass contact in pharmaceutical glass filling lines.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part application of U.S.application Ser. No. 13/780,754 filed Feb. 28, 2013 and entitled “GlassArticles With Low-Friction Coatings”, which claims priority to U.S.Provisional Patent Application No. 61/604,220 filed Feb. 28, 2012 andentitled “Glass Containers with a Surface Treatment that Enhances GlassReliability and Methods for Manufacturing the Same,” and to U.S.Provisional Patent Application No. 61/665,682 filed Jun. 28, 2012 andentitled “Delamination Resistant Glass Containers with Heat ResistantCoatings”, all of which are incorporated by reference herein in theirentirety.

BACKGROUND

Field

The present specification generally relates to pharmaceutical glasscontainers and, more specifically, to pharmaceutical glass containerswhich greatly reduce particle generation during processing, for example,during processing in pharmaceutical filling lines

Technical Background

Particle contamination, especially in parenteral drugs, poses a risk topatient safety and, despite being monitored closely duringpharmaceutical manufacturing, glass and metal particles continue to be aleading cause of parenteral drug recalls. With traditional glasscontainers, glass-to-glass contact produces significant quantities ofparticle of various sizes in the most sensitive portion of the fillingprocess (i.e., prior to container closure).

During processing in bulk, high speed pharmaceutical filling lines,conventional borosilicate glass containers are subjected to systematicglass to glass contact due to the handling method designs. Operationssuch as loading, accumulation, rotary drives, star wheels andsingulation place containers under load while they are in contact withone another. A number of the operations take place following washing,but before capping where the container is susceptible to glass to glassto damage. Furthermore, the glass is depyrogenated and cleaned, furtherincreasing the surface coefficient of friction and susceptibility andseverity of the damage. The damage that is caused from glass to glasscontact results in glass particle generation. Depending on the nature ofthe damage, impact loads and presence of pre-existing damage, glassparticles ranging from 1 to 120 μm can be generated. If these particlesare being generated in the filling line environment, there exists a riskthat the particles can contaminate open containers. The design of thefilling line area and laminar air flow does not fully prevent suchairborne contamination.

The United States Pharmacopoeia (USP) has defined limits on allowableparticle levels. The allowable level for visible particles is zero.Visible particles are defined by the ability for a certified operator todetect the particle in the solution with the unaided eye with specificlighting conditions. <USP 1 and USP 790>. Generally, particles in the 50to 150 μm range is the threshold for reliable visible detection. USP hasregulations for sub-visible particle levels as well. <USP 788> defineslevels of 600 and 6000 particles per dose for particles size >25 μmand >10 μm respectively. Particle generation in pharmaceutical fillinglines can make containers non-compliant with USP standards.

Accordingly, a need exists for improved pharmaceutical glass containerswhich reduce particle generation in pharmaceutical filling lines.

SUMMARY

Embodiments of the present disclosure are directed to pharmaceuticalcoatings, which prevent glass particles from being generated duringprocessing, for example, during processing in the pharmaceutical fillingline area. The coating additionally improves machinability duringfilling line processing and reduces catastrophic break events which tendto contaminate adjacent containers and the filling line environment.

According to one embodiment, a coated glass article is provided. Acoated glass article comprising a glass body comprising glass and havinga first surface and a second surface opposite the first surface, whereinthe first surface is an exterior surface of the glass body, and acoating disposed on at least a portion of the exterior surface of theglass body. The coated glass article reduces particle generation whenthe coated glass article undergoes processing, wherein the coated glassarticle demonstrates at least a 50% reduction in average particle countfor generated sub-visible glass particles compared to an averageparticle count of generated sub-visible glass particles by an uncoatedglass article that undergoes processing, wherein the average particlecount is computed using light obscuration according to United StatesPharmacopoeia Standard 788.

According to another embodiment, the coated glass article comprises aglass body comprising glass and having a first surface and a secondsurface opposite the first surface, wherein the first surface is anexterior surface of the glass body, and a coating disposed on at least aportion of the exterior surface of the glass body, the coatingcomprising a polymer chemical composition. The coated glass articlereduces glass particle formation caused by non-breakage inducing glasscontact in pharmaceutical glass filling lines. The reduction in glassparticle formation is defined as follows: wherein an average particlecount of generated sub-visible glass particles having a size of 50 μm orless is below allowable levels defined by United States PharmacopoeiaReference Standard 788, the average particle count being computed usinglight obscuration; and wherein the coated glass article demonstrates atleast a 50% reduction in average particle count for generatedsub-visible glass particles compared to an average particle count ofgenerated sub-visible glass particles by an uncoated glass article inthe pharmaceutical glass filling lines.

It is to be understood that both the foregoing general description andthe following detailed description describe various embodiments and areintended to provide an overview or framework for understanding thenature and character of the claimed subject matter. The accompanyingdrawings are included to provide a further understanding of the variousembodiments, and are incorporated into and constitute a part of thisspecification. The drawings illustrate the various embodiments describedherein, and together with the description serve to explain theprinciples and operations of the claimed subject matter.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically depicts a cross section of a glass container with alow-friction coating, according to one or more embodiments shown anddescribed herein;

FIG. 2 schematically depicts a cross section of a glass container with alow-friction coating comprising a polymer layer and a coupling agentlayer, according to one or more embodiments shown and described herein;

FIG. 3 schematically depicts a cross section of a glass container with alow-friction coating comprising a polymer layer, a coupling agent layer,and an interface layer, according to one or more embodiments shown anddescribed herein,

FIG. 4 shows an example of a diamine monomer chemical composition,according to one or more embodiments shown and described herein;

FIG. 5 shows an example of a diamine monomer chemical composition,according to one or more embodiments shown and described herein;

FIG. 6 depicts the chemical structures of monomers that may be used aspolyimide coatings applied to glass containers, according to one or moreembodiments shown and described herein;

FIG. 7 is a flow diagram of one embodiment of a method for forming aglass container with a low-friction coating, according to one or moreembodiments shown and described herein;

FIG. 8 schematically depicts the steps of the flow diagram of FIG. 7,according to one or more embodiments shown and described herein;

FIG. 9 schematically depicts a testing jig for determining thecoefficient of friction between two surfaces, according to one or moreembodiments shown and described herein;

FIG. 10 schematically depicts an apparatus for testing the mass loss ofa glass container, according to one or more embodiments shown anddescribed herein;

FIG. 11 graphically depicts the light transmittance data for coated anduncoated vials measured in the visible light spectrum from 400-700 nm,according to one or more embodiments shown and described herein;

FIG. 12 graphically depicts the failure probability as a function ofapplied load in a horizontal compression test for vials, according toone or more embodiments shown and described herein;

FIG. 13 contains a Table reporting the load and measured coefficient offriction for Schott Type 1B glass vials and vials formed from aReference Glass Composition that were ion exchanged and coated,according to one or more embodiments shown and described herein;

FIG. 14 graphically depicts the failure probability as a function ofapplied stress in four point bending for tubes formed from a ReferenceGlass Composition in as received condition, in ion exchanged condition(uncoated), in ion exchanged condition (coated and abraded), in ionexchanged condition (uncoated and abraded) and for tubes formed fromSchott Type 1B glass in as received condition and in ion exchangedcondition, according to one or more embodiments shown and describedherein;

FIG. 15 depicts gas chromatograph-mass spectrometer output data for aAPS/NOVASTRAT® 800 coating, according to one or more embodiments shownand described herein;

FIG. 16 depicts gas chromatography-mass spectrometer output data for aDC806A coating, according to one or more embodiments shown and describedherein;

FIG. 17 contains a Table reporting different low-friction coatingcompositions which were tested under lyophilization conditions,according to one or more embodiments shown and described herein;

FIG. 18 contains a chart reporting the coefficient of friction for bareglass vials and vials having a silicone resin coating tested in avial-on-vial jig, according to one or more embodiments shown anddescribed herein;

FIG. 19 contains a chart reporting the coefficient of friction for vialscoated with an APS/Kapton polyimide coating and abraded multiple timesunder different applied loads in a vial-on-vial jig, according to one ormore embodiments shown and described herein;

FIG. 20 contains a chart reporting the coefficient of friction for vialscoated with an APS coating and abraded multiple times under differentapplied loads in a vial-on-vial jig, according to one or moreembodiments shown and described herein;

FIG. 21 contains a chart reporting the coefficient of friction for vialscoated with an APS/Kapton polyimide coating and abraded multiple timesunder different applied loads in a vial-on-vial jig after the vials wereexposed to 300° C. for 12 hours, according to one or more embodimentsshown and described herein;

FIG. 22 contains a chart reporting the coefficient of friction for vialscoated with an APS coating and abraded multiple times under differentapplied loads in a vial-on-vial jig after the vials were exposed to 300°C. for 12 hours, according to one or more embodiments shown anddescribed herein;

FIG. 23 contains a chart reporting the coefficient of friction forSchott Type 1B vials coated with a Kapton polyimide coating and abradedmultiple times under different applied loads in a vial-on-vial jig,according to one or more embodiments shown and described herein;

FIG. 24 shows the coefficient of friction for APS/NOVASTRAT® 800 coatedvials before and after lyophilization, according to one or moreembodiments shown and described herein;

FIG. 25 graphically depicts the failure probability as a function ofapplied load in a horizontal compression test for vials, according toone or more embodiments shown and described herein;

FIG. 26 shows the coefficient of friction for APS/NOVASTRAT® 800 coatedvials before and after autoclaving, according to one or more embodimentsshown and described herein; and

FIG. 27 graphically depicts the coefficient of friction for coated glasscontainers exposed to different temperature conditions and for anuncoated glass container;

FIG. 28 contains a Table illustrating the change in the coefficient offriction with variations in the composition of the coupling agent of alow-friction coating applied to a glass container as described herein;

FIG. 29 graphically depicts the coefficient of friction, applied forceand frictive force for coated glass containers before and afterdepyrogenation;

FIG. 30 graphically depicts the coefficient of friction, applied forceand frictive force for coated glass containers for differentdepyrogenation conditions;

FIG. 31 shows a schematic diagram of reaction steps of a silane bondingto a substrate, according to one or more embodiments shown and describedherein;

FIG. 32 shows a schematic diagram of reaction steps of a polyimidebonding to a silane, according to one or more embodiments shown anddescribed herein;

FIG. 33 graphically depicts the coefficient of friction, scratchpenetration, applied normal force, and frictional force (y-ordinates) asa function of the length of the applied scratch (x-ordinate) for theas-coated vials of a Comparative Example;

FIG. 34 graphically depicts the coefficient of friction, scratchpenetration, applied normal force, and frictional force (y-ordinates) asa function of the length of the applied scratch (x-ordinate) for thethermally treated vials of a Comparative Example;

FIG. 35 graphically depicts the coefficient of friction, scratchpenetration, applied normal force, and frictional force (y-ordinates) asa function of the length of the applied scratch (x-ordinate) for theas-coated vials of a Comparative Example;

FIG. 36 graphically depicts the coefficient of friction, scratchpenetration, applied normal force, and frictional force (y-ordinates) asa function of the length of the applied scratch (x-ordinate) for thethermally treated vials of a Comparative Example;

FIG. 37 graphically depicts the coefficient of friction, applied forceand frictive force for coated glass containers before and afterdepyrogenation, according to one or more embodiments shown and describedherein;

FIG. 38 graphically depicts the failure probability as a function ofapplied load in a horizontal compression test for vials, according toone or more embodiments shown and described herein;

FIG. 39 graphically depicts the coefficient of friction, applied forceand frictive force for coated glass containers before and afterdepyrogenation, according to one or more embodiments shown and describedherein;

FIG. 40 graphically depicts the coefficient of friction after varyingheat treatment times, according to one or more embodiments shown anddescribed herein, according to one or more embodiments shown anddescribed herein;

FIG. 41 graphically depicts the coefficient of friction, applied forceand frictive force for coated glass containers before and afterdepyrogenation, according to one or more embodiments shown and describedherein;

FIG. 42 graphically depicts the failure probability as a function ofapplied load in a horizontal compression test for vials, according toone or more embodiments shown and described herein;

FIG. 43 shows a scanning electron microscope image of a coating,according to one or more embodiments shown and described herein;

FIG. 44 shows a scanning electron microscope image of a coating,according to one or more embodiments shown and described herein;

FIG. 45 shows a scanning electron microscope image of a coating,according to one or more embodiments shown and described herein; and

FIG. 46 graphically depicts the light transmittance data for coated anduncoated vials measured in the visible light spectrum from 400-700 nm,according to one or more embodiments shown and described herein.

FIG. 47 is a photograph of an uncoated borosilicate vial following afilling line trial.

FIG. 48 is a photograph of exemplary coated vials following a fillingline trial, according to one or more embodiments shown and describedherein.

FIG. 49A is an EDX plot of coated glass vial samples which undergo vialscratch testing as discussed in the Examples, according to one or moreembodiments shown and described herein.

FIG. 49B is an Energy Dispersive X-ray Spectroscopy (EDX) plot ofcomparative uncoated glass vial samples which undergo vial scratchtesting as discussed in the Examples.

FIG. 50 is a schematic depiction of a vial scratch test used to evaluateand characterize particle generation, according to one or moreembodiments shown and described herein.

FIG. 51 is a particle distribution determined from a debris fieldproduced from 1 mm scratches on uncoated vial samples at a scratch speedof 60 mm/min and scratch load between 1 to 30 N,

FIG. 52 is a particle distribution from a debris field produced from 1mm scratches on uncoated vial samples at a scratch load of 30 N and ascratch velocity in the range of 6 to 120 mm/min.

FIG. 53 is an SEM image of a debris field produced as uncoated vialsamples are subjected to a 30 N applied scratch load.

FIG. 54 is a Weibull plot showing the durability of coated glasscartridge samples following multiple scratches at loads of 1 to 30 N,according to one or more embodiments shown and described herein.

FIG. 55 is a Weibull plot showing the durability of a comparativesilicone coated cartridge samples following multiple scratches at loadsof 1 to 30 N.

FIG. 56 is an SEM image of a debris field produced when subjectinguncoated vials to a filling line trial.

FIG. 57 is a schematic illustration depicting moving vials sliding pastvials constrained by the inner guide on a rotary accumulator table.

FIG. 58 is a schematic illustration depicting a screw feeder deliveringvials that impact stationary vials on a stationary plate.

DETAILED DESCRIPTION

Reference will now be made in detail to various embodiments ofpharmaceutical glass containers, examples of which are schematicallydepicted in the figures and described below. Such coated glass articlesmay be glass containers suitable for use in various packagingapplications including, without limitation, as pharmaceutical packages.These pharmaceutical packages may or may not contain a pharmaceuticalcomposition. Various embodiments of the low-friction coatings, glassarticles with low-friction coatings, and methods for forming the samewill be described in further detail herein with specific reference tothe appended drawings. While embodiments of the low-friction coatingsdescribed herein are applied to the outer surface of a glass container,it should be understood that the low-friction coatings described may beused as a coating on a wide variety of materials, including non-glassmaterials and on substrates other than containers including, withoutlimitation, glass display panels and the like.

Generally, a low-friction coating may be applied to a surface of a glassarticle, such as a container that may be used as a pharmaceuticalpackage. The low-friction coating may provide advantageous properties tothe coated glass article such as a reduced coefficient of friction andincreased damage resistance. The reduced coefficient of friction mayimpart improved strength and durability to the glass article bymitigating frictive damage to the glass. Further, the low-frictioncoating may maintain the aforementioned improved strength and durabilitycharacteristics following exposure to elevated temperatures and otherconditions, such as those experienced during packaging and pre-packagingsteps utilized in packaging pharmaceuticals, such as, for example,depyrogenation, autoclaving and the like. Accordingly, the low-frictioncoatings and glass articles with the low-friction coating are thermallystable.

The low-friction coating may generally comprise a coupling agent, suchas a silane, and a polymer chemical composition, such as a polyimide. Insome embodiments, the coupling agent may be disposed in a coupling agentlayer positioned on the surface of the glass article and the polymerchemical composition may be disposed in a polymer layer positioned onthe coupling agent layer. In other embodiments, the coupling agent andthe polymer chemical composition may be mixed in a single layer.

FIG. 1 schematically depicts a cross section of a coated glass article,specifically a coated glass container 100. The coated glass container100 comprises a glass body 102 and a low-friction coating 120. The glassbody 102 has a glass container wall 104 extending between an exteriorsurface 108 (i.e., a first surface) and an interior surface 110 (i.e., asecond surface). The interior surface 110 of the glass container wall104 defines an interior volume 106 of the coated glass container 100. Alow-friction coating 120 is positioned on at least a portion of theexterior surface 108 of the glass body 102. In some embodiments, thelow-friction coating 120 may be positioned on substantially the entireexterior surface 108 of the glass body 102. The low-friction coating 120has an outer surface 122 and a glass body contacting surface 124 at theinterface of the glass body 102 and the low-friction coating 120. Thelow-friction coating 120 may be bonded to the glass body 102 at theexterior surface 108.

In one embodiment, the coated glass container 100 is a pharmaceuticalpackage. For example, the glass body 102 may be in the shape of a vial,ampoule, ampul, bottle, flask, phial, beaker, bucket, carafe, vat,syringe body, or the like. The coated glass container 100 may be usedfor containing any composition, and in one embodiment, may be used forcontaining a pharmaceutical composition. A pharmaceutical compositionmay include any chemical substance intended for use in the medicaldiagnosis, cure, treatment, or prevention of disease. Examples ofpharmaceutical compositions include, but are not limited to, medicines,drugs, medications, medicaments, remedies, and the like. Thepharmaceutical composition may be in the form of a liquid, solid, gel,suspension, powder, or the like.

Now referring to FIGS. 1 and 2, in one embodiment, the low-frictioncoating 120 comprises a bi-layered structure. FIG. 2 shows a crosssection of a coated glass container 100, where the low-friction coatingcomprises a polymer layer 170 and a coupling agent layer 180. A polymerchemical composition may be contained in polymer layer 170 and acoupling agent may be contained in a coupling agent layer 180. Thecoupling agent layer 180 may be in direct contact with the exteriorsurface 108 of the glass container wall 104. The polymer layer 170 maybe in direct contact with the coupling agent layer 180 and may form theouter surface 122 of the low-friction coating 120. In some embodimentsthe coupling agent layer 180 is bonded to the glass wall 104 and thepolymer layer 170 is bonded to the coupling agent layer 180 at aninterface 174. However, it should be understood that, in someembodiments, the low-friction coating 120 may not include a couplingagent, and the polymer chemical composition may be disposed in a polymerlayer 170 in direct contact with the exterior surface 108 of the of theglass container wall 104. In another embodiment, the polymer chemicalcomposition and coupling agent may be substantially mixed in a singlelayer. In some other embodiments, the polymer layer may be positionedover the coupling agent layer, meaning that the polymer layer 170 is inan outer layer relative to the coupling agent layer 180, and the glasswall 104. As used herein, a first layer positioned “over” a second layermeans that the first layer could be in direct contact with the secondlayer or separated from the second layer, such as with a third layerdisposed between the first and second layers.

Referring now to FIG. 3, in one embodiment, the low-friction coating 120may further comprise an interface layer 190 positioned between thecoupling agent layer 180 and the polymer layer 170. The interface layer190 may comprise one or more chemical compositions of the polymer layer170 bound with one or more of the chemical compositions of the couplingagent layer 180. In this embodiment, the interface of the coupling agentlayer and polymer layer forms an interface layer 190 where bondingoccurs between the polymer chemical composition and the coupling agent.However, it should be understood that in some embodiments, there may beno appreciable layer at the interface of the coupling agent layer 180and polymer layer 170 where the polymer and coupling agent arechemically bound to one another as described above with reference toFIG. 2.

The low-friction coating 120 applied to the glass body 102 may have athickness of less than about 100 μm or even less than or equal to about1 μm. In some embodiments, the thickness of the low-friction coating 120may be less than or equal to about 100 nm thick. In other embodiments,the low-friction coating 120 may be less than about 90 nm thick, lessthan about 80 nm thick, less than about 70 nm thick, less than about 60nm thick, less than about 50 nm, or even less than about 25 nm thick. Insome embodiments, the low-friction coating 120 may not be of uniformthickness over the entirety of the glass body 102. For example, thecoated glass container 100 may have a thicker low-friction coating 120in some areas, due to the process of contacting the glass body 102 withone or more coating solutions that form the low-friction coating 120. Insome embodiments, the low-friction coating 120 may have a non-uniformthickness. For example, the coating thickness may be varied overdifferent regions of a coated glass container 100, which may promoteprotection in a selected region.

In embodiments which include at least two layers, such as the polymerlayer 170, interface layer 190, and/or coupling agent layer 180, eachlayer may have a thickness of less than about 100 μm or even less thanor equal to about 1 μm. In some embodiments, the thickness of each layermay be less than or equal to about 100 nm. In other embodiments, eachlayer may be less than about 90 nm thick, less than about 80 nm thick,less than about 70 nm thick, less than about 60 nm thick, less thanabout 50 nm, or even less than about 25 nm thick.

As noted herein, in some embodiments, the low-friction coating 120comprises a coupling agent. The coupling agent may improve the adherenceor bonding of the polymer chemical composition to the glass body 102,and is generally disposed between the glass body 102 and the polymerchemical composition or mixed with the polymer chemical composition.Adhesion, as used herein, refers to the strength of adherence or bondingof the low friction coating prior to and following a treatment appliedto the coated glass container, such as a thermal treatment. Thermaltreatments include, without limitation, autoclaving, depyrogenation,lyophilization, or the like.

In one embodiment, the coupling agent may comprise at least one silanechemical composition. As used herein, a “silane” chemical composition isany chemical composition comprising a silane moiety, includingfunctional organosilanes, as well as silanols formed from silanes inaqueous solutions. The silane chemical compositions of the couplingagent may be aromatic or aliphatic. In some embodiments, the at leastone silane chemical composition may comprise an amine moiety, such as aprimary amine moiety or a secondary amine moiety. Furthermore, thecoupling agent may comprise hydrolysates and/or oligomers of suchsilanes, such as one or more silsesquioxane chemical compositions thatare formed from the one or more silane chemical compositions. Thesilsesquioxane chemical compositions may comprise a full cage structure,partial cage structure, or no cage structure.

The coupling agent may comprise any number of different chemicalcompositions, such as one chemical composition, two different chemicalcompositions, or more than two different chemical compositions includingoligomers formed from more than one monomeric chemical composition. Inone embodiment, the coupling agent may comprise at least one of (1) afirst silane chemical composition, hydrolysate thereof, or oligomerthereof, and (2) a chemical composition formed from the oligomerizationof at least the first silane chemical composition and a second silanechemical composition. In another embodiment, the coupling agentcomprises a first and second silane. As used herein, a “first” silanechemical composition and a “second” silane chemical composition aresilanes having different chemical compositions. The first silanechemical composition may be an aromatic or an aliphatic chemicalcomposition, may optionally comprise an amine moiety, and may optionallybe an alkoxysilane. Similarly, the second silane chemical compositionmay be an aromatic or an aliphatic chemical composition, may optionallycomprise an amine moiety, and may optionally be an alkoxysilane.

For example, in one embodiment, only one silane chemical composition isapplied as the coupling agent. In such an embodiment, the coupling agentmay comprise a silane chemical composition, hydrolysate thereof, oroligomer thereof.

In another embodiment, multiple silane chemical compositions may beapplied as the coupling agent. In such an embodiment, the coupling agentmay comprise at least one of (1) a mixture of the first silane chemicalcomposition and a second silane chemical composition, and (2) a chemicalcomposition formed from the oligomerization of at least the first silanechemical composition and the second silane chemical composition.

Referring to the embodiments described above, the first silane chemicalcomposition, second silane chemical composition, or both, may bearomatic chemical compositions. As used herein, an aromatic chemicalcomposition contains one or more six-carbon rings characteristic of thebenzene series and related organic moieties. The aromatic silanechemical composition may be an alkoxysilane such as, but not limited to,a dialkoxysilane chemical composition, hydrolysate thereof, or oligomerthereof, or a trialkoxysilane chemical composition, hydrolysate thereof,or oligomer thereof. In some embodiments, the aromatic silane maycomprise an amine moiety, and may be an alkoxysilane comprising an aminemoiety. In another embodiment, the aromatic silane chemical compositionmay be an aromatic alkoxysilane chemical composition, an aromaticacyloxysilane chemical composition, an aromatic halogen silane chemicalcomposition, or an aromatic aminosilane chemical composition. In anotherembodiment, the aromatic silane chemical composition may be selectedfrom the group consisting of aminophenyl, 3-(m-aminophenoxy) propyl,N-phenylaminopropyl, or (chloromethy) phenyl substituted alkoxy,acyloxy, halogen, or amino silanes. For example, the aromaticalkoxysilane may be, but is not limited to, aminophenyltrimethoxy silane(sometimes referred to herein as “APhTMS”), aminophenyldimethoxy silane,aminophenyltriethoxy silane, aminophenyldiethoxy silane,3-(m-aminophenoxy) propyltrimethoxy silane, 3-(m-aminophenoxy)propyldimethoxy silane, 3-(m-aminophenoxy) propyltriethoxy silane,3-(m-aminophenoxy) propyldiethoxy silane,N-phenylaminopropyltrimethoxysilane, N-phenylaminopropyldimethoxysilane,N-phenylaminopropyltriethoxysilane, N-phenylaminopropyldiethoxysilane,hydrolysates thereof, or oligomerized chemical composition thereof. Inan exemplary embodiment, the aromatic silane chemical composition may beaminophenyltrimethoxy silane.

Referring again to the embodiments described above, the first silanechemical composition, second silane chemical composition, or both, maybe aliphatic chemical compositions. As used herein, an aliphaticchemical composition is non-aromatic, such as a chemical compositionhaving an open chain structure, such as, but not limited to, alkanes,alkenes, and alkynes. For example, in some embodiments, the couplingagent may comprise a chemical composition that is an alkoxysilane andmay be an aliphatic alkoxysilane such as, but not limited to, adialkoxysilane chemical composition, a hydrolysate thereof, or anoligomer thereof, or a trialkoxysilane chemical composition, ahydrolysate thereof, or an oligomer thereof. In some embodiments, thealiphatic silane may comprise an amine moiety, and may be analkoxysilane comprising an amine moiety, such as anaminoalkyltrialkoxysilane. In one embodiment, an aliphatic silanechemical composition may be selected from the group consisting of3-aminopropyl, N-(2-aminoethyl)-3-aminopropyl, vinyl, methyl,N-phenylaminopropyl, (N-phenylamino)methyl,N-(2-Vinylbenzylaminoethyl)-3-aminopropyl substituted alkoxy, acyloxy,halogen, or amino silanes, hydrolysates thereof, or oligomers thereof.Aminoalkyltrialkoxysilanes, include, but are not limited to,3-aminopropyltrimethoxy silane (sometimes referred to herein as “GAPS”),3-aminopropyldimethoxy silane, 3-aminopropyltriethoxy silane,3-aminopropyldiethoxy silane,N-(2-aminoethyl)-3-aminopropyltrimethoxysilane,N-(2-aminoethyl)-3-aminopropyldimethoxysilane,N-(2-aminoethyl)-3-aminopropyltriethoxysilane,N-(2-aminoethyl)-3-aminopropyldiethoxysilane, hydrolysates thereof, andoligomerized chemical composition thereof. In other embodiments, thealiphatic alkoxysilane chemical composition may not contain an aminemoiety, such as an alkyltrialkoxysilane or alkylbialkoxysilane. Suchalkyltrialkoxysilanes or alkylbialkoxysilanes include, but are notlimited to, vinyltrimethoxy silane, vinyldimethoxy silane,vinyltriethoxy silane, vinyldiethoxy silane, methyltrimethoxysilane,methyltdimethoxysilane, methyltriethoxysilane, methyldiethoxysilane,hydrolysates thereof, or oligomerized chemical composition thereof. Inan exemplary embodiment, the aliphatic silane chemical composition is3-aminopropyltrimethoxy silane.

It has been found that forming the coupling agent from combinations ofdifferent chemical compositions, particularly combinations of silanechemical compositions, may improve the thermal stability of thelow-friction coating 120. For example, it has been found thatcombinations of aromatic silanes and aliphatic silanes, such as thosedescribed above, improve the thermal stability of the low-frictioncoating, thereby producing a coating which retains its the mechanicalproperties, such as coefficient of friction and adhesion performancefollowing a heat treatment at elevated temperatures. Accordingly, in oneembodiment the coupling agent comprises a combination of aromatic andaliphatic silanes. In these embodiments, the ratio of aliphatic silanesto aromatic silanes (aliphatic:aromatic) may be from about 1:3 to about1:0.2. If the coupling agent comprises two or more chemical composition,such as at least an aliphatic silane and an aromatic silane, the ratioby weight of the two chemical compositions may be any ratio, such as aweight ratio of a first silane chemical composition to a second silanechemical composition (first silane:second silane) of about 0.1:1 toabout 10:1. For example, in some embodiments the ration may be from0.5:1 to about 2:1, such as 2:1, 1:1, 0.5:1. In some embodiments, thecoupling agent may comprise combinations of multiple aliphatic silanesand/or multiple aromatic silanes, which could be applied to the glasscontainer in one or multiple steps with or without organic or inorganicfillers. In some embodiments, the coupling agent comprises oligomers,such as silsesquioxanes, formed from both the aliphatic and aromaticsilanes.

In an exemplary embodiment, the first silane chemical composition is anaromatic silane chemical composition and the second silane chemicalcomposition is an aliphatic silane chemical composition. In oneexemplary embodiment, the first silane chemical composition is anaromatic alkoxysilane chemical composition comprising at least one aminemoiety and the second silane chemical composition is an aliphaticalkoxysilane chemical composition comprising at least one amine moiety.In another exemplary embodiment, the coupling agent comprises anoligomer of one or more silane chemical compositions, wherein theoligomer is a silsesquioxane chemical composition and at least one ofthe silane chemical compositions comprises at least one aromatic moietyand at least one amine moiety. In one particular exemplary embodiment,the first silane chemical composition is aminophenyltrimethoxy silaneand the second silane chemical composition is 3-aminopropyltrimethoxysilane. The ratio of aromatic silane to aliphatic silane may be about1:1. In another particular exemplary embodiment, the coupling agentcomprises an oligomer formed from aminophenyltrimethoxy and3-aminopropyltrimethoxy. In another embodiment, the coupling agent maycomprise both a mixture of aminophenyltrimethoxy and3-aminopropyltrimethoxy and oligomers formed from the two.

In another embodiment, the coupling agent may comprise a chemicalcomposition that is an aminoalkylsilsesquioxane. In one embodiment thecoupling agent comprises aminopropylsilsesquioxane (APS) oligomer(commercially available as an aqueous solution from Gelest).

In one embodiment, the aromatic silane chemical composition is achlorosilane chemical composition.

In another embodiment, the coupling agent may comprise chemicalcomposition that are hydrolyzed analogs of aminoalkoxysilanes such as,but not limited to, (3-Aminopropyl)silantriol,N-(2-Aminoethyl)-3-aminopropyl-silantriol and/or mixtures thereof.

In another embodiment, the coupling agent may be an inorganic material,such as metal and/or a ceramic film. Non-limiting examples of suitableinorganic materials used as the coupling agent include titanates,zirconates, tin, titanium, and/or oxides thereof.

In one embodiment, the coupling agent is applied to the exterior surface108 of the glass body 102 by contacting with the diluted coupling agentby a submersion process. The coupling agent may be mixed in a solventwhen applied to the glass body 102. In another embodiment, the couplingagent may be applied to the glass body 102 by a spray or other suitablemeans. The glass body 102 with coupling agent may then be dried ataround 120° C. for about 15 min, or any time and temperature sufficientto adequately liberate the water and/or other organic solvents presenton the exterior surface 108 of the glass container wall 104.

Referring to FIG. 2, in one embodiment, the coupling agent is positionedon the glass container as a coupling agent layer 180 and is applied as asolution comprising about 0.5 wt % of a first silane and about 0.5 wt %of a second silane (total 1 wt % silane) mixed with at least one ofwater and an organic solvent, such as, but not limited to, methanol.However, it should be understood that the total silane concentration inthe solution may be more or less than about 1 wt %, such as from about0.1 wt % to about 10 wt %, from about 0.3 wt % to about 5.0 wt %, orfrom about 0.5 wt % to about 2.0 wt %. For example, in one embodiment,the weight ratio of organic solvent to water (organic solvent:water) maybe from about 90:10 to about 10:90, and, in one embodiment, may be about75:25. The weight ratio of silane to solvent may affect the thickness ofthe coupling agent layer, where increased percentages of silane chemicalcomposition in the coupling agent solution may increase the thickness ofthe coupling agent layer 180. However, it should be understood thatother variables may affect the thickness of the coupling agent layer 180such as, but not limited, the specifics of the dip coating process, suchas the withdraw speed from the bath. For example, a faster withdrawspeed may form a thinner coupling agent layer 180.

In another embodiment, the coupling agent layer 180 may be applied as asolution comprising 0.1 vol % of a commercially availableaminopropylsilsesquioxane oligomer. Coupling agent layer solutions ofother concentrations may be used, including but not limited to,0.01-10.0 vol % aminopropylsilsesquioxane oligomer solutions.

As noted herein, the low friction coating also includes a polymerchemical composition. The polymer chemical composition may be athermally stable polymer or mixture of polymers, such as but not limitedto, polyimides, polybenzimidazoles, polysulfones, polyetheretheketones,polyetherimides, polyamides, polyphenyls, polybenzothiazoles,polybenzoxazoles, polybisthiazoles, and polyaromatic heterocyclicpolymers with and without organic or inorganic fillers. The polymerchemical composition may be formed from other thermally stable polymers,such as polymers that do not degrade at temperatures in the range offrom 200° C. to 400° C., including 250° C., 300° C., and 350° C. Thesepolymers may be applied with or without a coupling agent.

In one embodiment, the polymer chemical composition is a polyimidechemical composition. If the low-friction coating 120 comprises apolyimide, the polyimide composition may be derived from a polyamicacid, which is formed in a solution by the polymerization of monomers.One such polyamic acid is NOVASTRAT® 800 (commercially available fromNeXolve). A curing step imidizes the polyamic acid to form thepolyimide. The polyamic acid may be formed from the reaction of adiamine monomer, such as a diamine, and an anhydride monomer, such as adianhydride. As used herein, polyimide monomers are described as diaminemonomers and dianhydride monomers. However, it should be understood thatwhile a diamine monomer comprises two amine moieties, in the descriptionthat follows, any monomer comprising at least two amine moieties may besuitable as a diamine monomer. Similarly, it should be understood thatwhile a dianhydride monomer comprises two anhydride moieties, in thedescription that follows any monomer comprising at least two anhydridemoieties may be suitable as a dianhydride monomer. The reaction betweenthe anhydride moieties of the anhydride monomer and amine moieties ofthe diamine monomer forms the polyamic acid. Therefore, as used herein,a polyimide chemical composition that is formed from the polymerizationof specified monomers refers to the polyimide that is formed followingthe imidization of a polyamic acid that is formed from those specifiedmonomers. Generally, the molar ratio of the total anhydride monomers anddiamine monomers may be about 1:1. While the polyimide may be formedfrom only two distinct chemical compositions (one anhydride monomer andone diamine monomer), at least one anhydride monomer may be polymerizedand at least one diamine monomer may be polymerized to from thepolyimide. For example, one anhydride monomer may be polymerized withtwo different diamine monomers. Any number of monomer speciecombinations may be used. Furthermore, the ratio of one anhydridemonomer to a different anhydride monomer, or one or more diamine monomerto a different diamine monomer may be any ratio, such as between about1:0.1 to 0.1:1, such as about 1:9, 1:4, 3:7, 2:3, 1:1, 3:2, 7:3, 4:1 or1:9.

The anhydride monomer from which, along with the diamine monomer, thepolyimide is formed may comprise any anhydride monomer. In oneembodiment, the anhydride monomer comprises a benzophenone structure. Inan exemplary embodiment, benzophenone-3,3′,4,4′-tetracarboxylicdianhydride may be at least one of the anhydride monomer from which thepolyimide is formed. In other embodiments, the diamine monomer may havean anthracene structure, a phenanthrene structure, a pyrene structure,or a pentacene structure, including substituted versions of the abovementioned dianhydrides.

The diamine monomer from which, along with the anhydride monomer, thepolyimide is formed may comprise any diamine monomer. In one embodiment,the diamine monomer comprises at least one aromatic ring moiety. FIGS. 4and 5 show examples of diamine monomers that, along with one or moreselected anhydride monomer, may form the polyimide comprising thepolymer chemical composition. The diamine monomer may have one or morecarbon molecules connecting two aromatic ring moieties together, asshown in FIG. 5, wherein R of FIG. 5 corresponds to an alkyl moietycomprising one or more carbon atoms. Alternatively, the diamine monomermay have two aromatic ring moieties that are directly connected and notseparated by at least one carbon molecule, as shown in FIG. 4. Thediamine monomer may have one or more alkyl moieties, as represented byR′ and R″ in FIGS. 4 and 5. For example, in FIGS. 4 and 5, R′ and R″ mayrepresent an alkyl moiety such as methyl, ethyl, propyl, or butylmoieties, connected to one or more aromatic ring moieties. For example,the diamine monomer may have two aromatic ring moieties wherein eacharomatic ring moiety has an alkyl moiety connected thereto and adjacentan amine moiety connected to the aromatic ring moiety. It should beunderstood that R′ and R″, in both FIGS. 4 and 5, may be the samechemical moiety or may be different chemical moieties. Alternatively, R′and/or R″, in both FIGS. 4 and 5, may include a hydrogen group insteadof an alkyl moiety.

Two different chemical compositions of diamine monomers may form thepolyimide. In one embodiment, a first diamine monomer comprises twoaromatic ring moieties that are directly connected and not separated bya linking carbon molecule, and a second diamine monomer comprises twoaromatic ring moieties that are connected with at least one carbonmolecule connecting the two aromatic ring moieties. In one exemplaryembodiment, the first diamine monomer, the second diamine monomer, andthe anhydride monomer have a molar ratio (first diamine monomer:seconddiamine monomer:anhydride monomer) of about 0.465:0.035:0.5. However,the ratio of the first diamine monomer and the second diamine monomermay vary in a range of about 0.01:0.49 to about 0.40:0.10, while theanhydride monomer ratio remains at about 0.5.

In one embodiment, the polyimide composition is formed from thepolymerization of at least a first diamine monomer, a second diaminemonomer, and an anhydride monomer, wherein the first and second diaminemonomers are different chemical compositions. In one embodiment, theanhydride monomer is a benzophenone, the first diamine monomer comprisestwo aromatic rings directly bonded together, and the second diaminemonomer comprises two aromatic rings bonded together with at least onecarbon molecule connecting the first and second aromatic rings. Thefirst diamine monomer, the second diamine monomer, and the anhydridemonomer may have a molar ratio (first diamine monomer:second diaminemonomer:anhydride monomer) of about 0.465:0.035:0.5.

In an exemplary embodiment, the first diamine monomer is ortho-Tolidine,the second diamine monomer is 4,4′-methylene-bis(2-methylaniline), andthe anhydride monomer is benzophenone-3,3′,4,4′-tetracarboxylicdianhydride. The first diamine monomer, the second diamine monomer, andthe anhydride monomer may have a molar ratio (first diaminemonomer:second diamine monomer:anhydride monomer) of about0.465:0.035:0.5.

In some embodiments, the polyimide may be formed from the polymerizationof one or more of: bicyclo[2.2.1]heptane-2,3,5,6-tetracarboxylicdianhydride, cyclopentane-1,2,3,4-tetracarboxylic 1,2;3,4-dianhydride,bicyclo[2.2.2]octane-2,3,5,6-tetracarboxylic dianhydride,4arH,8acH)-decahydro-1t,4t:5c,8c-dimethanonaphthalene-2t,3t,6c,7c-tetracarboxylic2,3:6,7-dianhydride, 2c,3c,6c,7c-tetracarboxylic 2,3:6,7-dianhydride,5-endo-carboxymethylbicyclo[2.2.1]-heptane-2-exo,3-exo,5-exo-tricarboxylicacid 2,3:5,5-dianhydride,5-(2,5-Dioxotetrahydro-3-furanyl)-3-methyl-3-cyclohexene-1,2-dicarboxylicanhydride, isomers of Bis(aminomethyl)bicyclo[2.2.1]heptane, or4,4′-Methylenebis(2-methylcyclohexylamine), Pyromellitic dianhydride(PMDA) 3,3′,4,4′-Biphenyl dianhydride (4,4′-BPDA),3,3′,4,4′-Benzophenone dianhydride (4,4′-BTDA), 3,3′,4,4′-Oxydiphthalicanhydride (4,4′-ODPA), 1,4-Bis(3,4-dicarboxyl-phenoxy)benzenedianhydride (4,4′-HQDPA), 1,3-Bis (2,3-dicarboxyl-phenoxy)benzenedianhydride (3,3′-HQDPA), 4,4′-Bis(3,4-dicarboxylphenoxyphenyl)-isopropylidene dianhydride (4,4′-BPADA),4,4′-(2,2,2-Trifluoro-1-pentafluorophenylethylidene) diphthalicdianhydride (3FDA), 4,4′-Oxydianiline (ODA), m-Phenylenediamine (MPD),p-Phenylenediamine (PPD), m-Toluenediamine (TDA),1,4-Bis(4-aminophenoxy)benzene (1,4,4-APB),3,3′-(m-Phenylenebis(oxy))dianiline (APB),4,4′-Diamino-3,3′-dimethyldiphenylmethane (DMMDA),2,2′-Bis(4-(4-aminophenoxy)phenyl)propane (BAPP), 1,4-Cyclohexanediamine2,2′-Bis[4-(4-aminophenoxy) phenyl]hexafluoroisopropylidene (4-BDAF),6-Amino-1-(4′-aminophenyl)-1,3,3-trimethylindane (DAPI), Maleicanhydride (MA), Citraconic anhydride (CA), Nadic anhydride (NA),4-(Phenylethynyl)-1,2-benzenedicarboxylic acid anhydride (PEPA),4,4′-diaminobenzanilide (DABA),4,4′-(hexafluoroisopropylidene)di-phthalicanhydride (6-FDA),Pyromellitic dianhydride, benzophenone-3,3′,4,4′-tetracarboxylicdianhydride, 3,3′,4,4′-biphenyltetracarboxylic dianhydride,4,4′-(hexafluoroisopropylidene)diphthalic anhydride,perylene-3,4,9,10-tetracarboxylic dianhydride, 4,4′-oxydiphthalicanhydride, 4,4′-(hexafluoroisopropylidene)diphthalic anhydride,4,4′-(4,4′-Isopropylidenediphenoxy)bis(phthalic anhydride),1,4,5,8-Naphthalenetetracarboxylic dianhydride,2,3,6,7-Naphthalenetetracarboxylic dianhydride, as well as thosematerials described in U.S. Pat. Nos. 7,619,042, 8,053,492, 4,880,895,6,232,428, 4,595,548, WO Pub. No. 2007/016516, U.S. Pat. Pub. No.2008/0214777, U.S. Pat. Nos. 6,444,783, 6,277,950, and 4,680,373. FIG. 6depicts the chemical structure of some suitable monomers that may beused to form a polyimide coating applied to the glass body 102. Inanother embodiment, the polyamic acid solution from which the polyimideis formed may comprise poly (pyromelliticdianhydride-co-4,4′-oxydianiline) amic acid (commercially available fromAldrich).

In another embodiment, the polymer chemical composition may comprise afluoropolymer. The fluoropolymer may be a copolymer wherein bothmonomers are highly fluorinated. Some of the monomers of thefluoropolymer may be fluoroethylene. In one embodiment, the polymerchemical composition comprises an amorphous fluoropolymer, such as, butnot limited to, Teflon AF (commercially available from DuPont). Inanother embodiment, the polymer chemical composition comprisesperfluoroalkoxy (PFA) resin particles, such as, but not limited to,Teflon PFA TE-7224 (commercially available from DuPont).

In another embodiment, the polymer chemical composition may comprise asilicone resin. The silicone resin may be a highly branched3-dimensional polymer which is formed by branched, cage-likeoligosiloxanes with the general formula of R_(n)Si(X)_(m)O_(y), where Ris a non reactive substituent, usually methyl or phenyl, and X is OH orH. While not wishing to be bound by theory, it is believed that curingof the resin occurs through a condensation reaction of Si—OH moietieswith a formation of Si—O—Si bonds. The silicone resin may have at leastone of four possible functional siloxane monomeric units, which includeM-resins, D-resins, T-resins, and Q-resins, wherein M-resins refer toresins with the general formula R₃SiO, D-resins refer to resins with thegeneral formula R₂SiO₂, T-resins refer to resins with the generalformula RSiO₃, and Q-resins refer to resins with the general formulaSiO₄ (a fused quartz). In some embodiments resins are made of D and Tunits (DT resins) or from M and Q units (MQ resins). In otherembodiments, other combinations (MDT, MTQ, QDT) are also used.

In one embodiment, the polymer chemical composition comprisesphenylmethyl silicone resins due to their higher thermal stabilitycompared to methyl or phenyl silicone resins. The ratio of phenyl tomethyl moieties in the silicone resins may be varied in the polymerchemical composition. In one embodiment, the ratio of phenyl to methylis about 1.2. In another embodiment, the ratio of phenyl to methyl isabout 0.84. In other embodiments, the ratio of phenyl to methyl moietiesmay be about 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.3, 1.4, or 1.5. In oneembodiment, the silicone resin is DC 255 (commercially available fromDow Corning). In another embodiment, the silicone resin is DC806A(commercially available from Dow Corning). In other embodiments, thepolymer chemical composition may comprise any of the DC series resins(commercially available for Dow Corning), and/or Hardsil Series AP andAR resins (commercially available from Gelest). The silicone resins canbe used without coupling agent or with coupling agent.

In another embodiment, the polymer chemical composition may comprisesilsesquioxane-based polymers, such as but not limited to T-214(commercially available from Honeywell), SST-3M01 (commerciallyavailable from Gelest), POSS Imiclear (commercially available fromHybrid Plastics), and FOX-25 (commercially available from Dow Corning).In one embodiment, the polymer chemical composition may comprise asilanol moiety.

Referring again to FIGS. 1 and 2, the low-friction coating 120 may beapplied in a multi stage process, wherein the glass body 102 iscontacted with the coupling agent solution to form the coupling agentlayer 180 (as described above), and dried, and then contacted with apolymer chemical composition solution, such as a polymer or polymerprecursor solution, such as by a submersion process, or alternatively,the polymer chemical composition layer 170 may be applied by a spray orother suitable means, and dried, and then cured at high temperatures.Alternatively, if a coupling agent layer 180 is not used, the polymerchemical composition of the polymer layer 170 may be directly applied tothe exterior surface 108 of the glass body 102. In another embodiment,the polymer chemical composition and the coupling agent may be mixed inthe low-friction coating 120, and a solution comprising the polymerchemical composition and the coupling agent may be applied to the glassbody 102 in a single coating step.

In one embodiment, the polymer chemical composition comprises apolyimide wherein a polyamic acid solution is applied over the couplingagent layer 180. In other embodiments, a polyamic acid derivative may beused, such as, for example, a polyamic acid salt, a polyamic acid ester,or the like. In one embodiment, the polyamic acid solution may comprisea mixture of 1 vol % polyamic acid and 99 vol % organic solvent. Theorganic solvent may comprise a mixture of toluene and at least one ofN,N-Dimethylacetamide (DMAc), N,N-Dimethylformamide (DMF), and1-Methyl-2-pyrrolidinone (NMP) solvents, or a mixture thereof. In oneembodiment the organic solvent solution comprises about 85 vol % of atleast one of DMAc, DMF, and NMP, and about 15 vol % toluene. However,other suitable organic solvents may be used. The coated glass container100 may then be dried at around 150° C. for about 20 minutes, or anytime and temperature sufficient to adequately liberate the organicsolvent present in the low-friction coating 120.

In the layered low-friction coating embodiment, after the glass body 102is contacted with the coupling agent to form the coupling agent layer180 and polyamic acid solution to form the polymer layer 170, the coatedglass container 100 may be cured at high temperatures. The coated glasscontainer 100 may be cured at 300° C. for about 30 minutes or less, ormay be cured at a temperature higher than 300° C., such as at least 320°C., 340° C., 360° C., 380° C., or 400° C. for a shorter time. It isbelieved, without being bound by theory, that the curing step imidizesthe polyamic acid in the polymer layer 170 by reaction of carboxylicacid moieties and amide moieties to create a polymer layer 170comprising a polyimide. The curing may also promote bonds between thepolyimide and the coupling agent. The coated glass container 100 is thencooled to room temperature.

Furthermore, without being bound by limitation, it is believed that thecuring of the coupling agent, polymer chemical composition, or both,drives off volatile materials, such as water and other organicmolecules. As such, these volatile materials that are liberated duringcuring are not present when the article, if used as a container, isthermally treated (such as for depyrogenation) or contacted by thematerial in which it is a package for, such as a pharmaceutical. Itshould be understood that the curing processes described herein areseparate heating treatments than other heating treatments describedherein, such as those heating treatments similar or identical toprocesses in the pharmaceutical packaging industry, such asdepyrogenation or the heating treatments used to define thermalstability, as described herein.

The glass containers to which the low-friction coating 120 may beapplied may be formed from a variety of different glass compositions.The specific composition of the glass article may be selected accordingto the specific application such that the glass has a desired set ofphysical properties.

The glass containers may be formed from a glass composition which has acoefficient of thermal expansion in the range from about 25×10⁻⁷/° C. to80×10⁻⁷/° C. For example, in some embodiments described herein, theglass body 102 is formed from alkali aluminosilicate glass compositionswhich are amenable to strengthening by ion exchange. Such compositionsgenerally include a combination of SiO₂, Al₂O₃, at least one alkalineearth oxide, and one or more alkali oxides, such as Na₂O and/or K₂O. Insome of these embodiments, the glass composition may be free from boronand compounds containing boron. In some other embodiments the glasscompositions may further comprise minor amounts of one or moreadditional oxides such as, for example, SnO₂, ZrO₂, ZnO, TiO₂, As₂O₃, orthe like. These components may be added as fining agents and/or tofurther enhance the chemical durability of the glass composition. Inanother embodiment, the glass surface may comprise a metal oxide coatingcomprising SnO₂, ZrO₂, ZnO, TiO₂, As₂O₃, or the like

In some embodiments described herein, the glass body 102 is strengthenedsuch as by ion-exchange strengthening, herein referred to as“ion-exchanged glass”. For example, the glass body 102 may have acompressive stress of greater than or equal to about 300 MPa or evengreater than or equal to about 350 MPa. In some embodiments, thecompressive stress may be in a range from about 300 MPa to about 900MPa. However, it should be understood that, in some embodiments, thecompressive stress in the glass may be less than 300 MPa or greater than900 MPa. In some embodiments, the glass body 102 may have a depth oflayer greater than or equal to 20 μm. The compressive stress may bemeasured at the outer surface or the inner surface of the glass body,and the depth of layer may be measured from the outer surface or theinner surface inward toward the bulk of the glass body. In some of theseembodiments, the depth of layer may be greater than 50 μm or evengreater than or equal to 75 μm. In still other embodiments, the depth ofthe layer may be up to or greater than 100 μm. The ion-exchangestrengthening may be performed in a molten salt bath maintained attemperatures from about 350° C. to about 500° C. To achieve the desiredcompressive stress, the glass container (uncoated) may be immersed inthe salt bath for less than about 30 hours or even less than about 20hours. For example, in one embodiment the glass container is immersed ina 100% KNO₃ salt bath at 450° C. for about 8 hours.

In one particularly exemplary embodiment, the glass body 102 may beformed from an ion exchangeable glass composition described in U.S. Pat.No. 8,551,898 and entitled “Glass Compositions with Improved Chemicaland Mechanical Durability” assigned to Corning, Incorporated.

However it should be understood that the coated glass containers 100described herein may be formed from other glass compositions including,without limitation, ion-exchangeable glass compositions and non-ionexchangeable glass compositions. For example, in some embodiments theglass container may be formed from Type 1B glass compositions such as,for example, Schott Type 1B aluminosilicate glass.

In some embodiments described herein, the glass article may be formedfrom a glass composition which meets the criteria for pharmaceuticalglasses described by regulatory agencies such as the USP (United StatesPharmacopoeia), the EP (European Pharmacopeia), and the JP (JapanesePharmacopeia) based on their hydrolytic resistance. Per USP 660 and EP7, borosilicate glasses meet the Type I criteria and are routinely usedfor parenteral packaging. Examples of borosilicate glass include, butnot limited to Corning® Pyrex® 7740, 7800 and Wheaton 180, 200, and 400,Schott Duran, Schott Fiolax, KIMAX® N-51A, Gerrescheimer GX-51 Flint andothers. Soda-lime glass meets the Type III criteria and is acceptable inpackaging of dry powders which are subsequently dissolved to makesolutions or buffers. Type III glasses are also suitable for packagingliquid formulations that prove to be insensitive to alkali. Examples ofType III soda lime glass include Wheaton 800 and 900. De-alkalizedsoda-lime glasses have higher levels of sodium hydroxide and calciumoxide and meet the Type II criteria. These glasses are less resistant toleaching than Type I glasses but more resistant than Type III glasses.Type II glasses can be used for products that remain below a pH of 7 fortheir shelf life. Examples include ammonium sulfate treated soda limeglasses. These pharmaceutical glasses have varied chemical compositionsand have a coefficient of linear thermal expansion (CTE) in the range of20-85×10⁻⁷° C.⁻¹.

When the coated glass articles described herein are glass containers,the glass body 102 of the coated glass containers 100 may take on avariety of different forms. For example, the glass bodies describedherein may be used to form coated glass containers 100 such as vials,ampoules, cartridges, syringe bodies and/or any other glass containerfor storing pharmaceutical compositions. Moreover, the ability tochemically strengthen the glass containers prior to coating can beutilized to further improve the mechanical durability of the glasscontainers. Accordingly, it should be understood that, in at least oneembodiment, the glass containers may be ion exchange strengthened priorto application of the low-friction coating. Alternatively, otherstrengthening methods such as heat tempering, flame polishing, andlaminating, as described in U.S. Pat. No. 7,201,965, could be used tostrengthen the glass before coating.

In one embodiment, the coupling agent comprises a silane chemicalcomposition, such as an alkoxysilane, which may improve the adhesion ofthe polymer chemical composition to the glass body. Without being boundby theory, it is believed that alkoxysilane molecules hydrolyze rapidlyin water forming isolated monomers, cyclic oligomers, and largeintramolecular cyclics. In various embodiments, the control over whichspecies predominates may be determined by silane type, concentration,pH, temperature, storage condition, and time. For example, at lowconcentrations in aqueous solution, aminopropyltrialkoxysilane (APS) maybe stable and form trisilanol monomers and very low molecular weightoligomeric cyclics.

It is believed, still without being bound by theory, that the reactionof one or more silanes chemical compositions to the glass body mayinvolve several steps. As shown in FIG. 31, in some embodiments,following hydrolysis of the silane chemical composition, a reactivesilanol moiety may be formed, which can condense with other silanolmoieties, for example, those on the surface of a substrate, such as aglass body. After the first and second hydrolysable moieties arehydrolyzed, a condensation reaction may be initialized. In someembodiments, the tendency toward self condensation can be controlled byusing fresh solutions, alcoholic solvents, dilution, and by carefulselection of pH ranges. For example, silanetriols are most stable at pH3-6, but condense rapidly at pH 7-9.3, and partial condensation ofsilanol monomers may produce silsesquioxanes. As shown in FIG. 31, thesilanol moieties of the formed species may form hydrogen bonds withsilanol moieties on the substrate, and during drying or curing acovalent bond may be formed with the substrate with elimination ofwater. For example, a moderate cure cycle (110° C. for 15 min) may leavesilanol moieties remaining in free form and, along with any silaneorganofunctionality, may bond with the subsequent topcoat, providingimproved adhesion.

In some embodiments, the one or more silane chemical compositions of thecoupling agent may comprise an amine moiety. Still without being boundby theory, it is believed that this amine moiety may act as a basecatalyst in the hydrolysis and co-condensation polymerization andenhance the adsorption rate of the silanes having an amine moiety on aglass surface. It may also create a high pH (9.0-10.0) in aqueoussolution that conditions the glass surface and increases density ofsurface silanol moieties. Strong interaction with water and proticsolvents maintains solubility and stability of a silane having an aminemoiety chemical composition, such as APS.

In an exemplary embodiment, the glass body may comprise ion-exchangedglass and the coupling agent may be a silane. In some embodiments,adhesion of the low-friction coating to an ion-exchanged glass body maybe stronger than adhesion of the low-friction coating to anon-ion-exchanged glass body. It is believed, without being bound bytheory, that any of several aspects of ion-exchanged glass may promotebonding and/or adhesion, as compared with non-ion-exchanged glass.First, ion-exchanged glass may have enhanced chemical/hydrolyticstability that may affect stability of the coupling agent and/or itsadhesion to glass surface. Non-ion-exchanged glass typically hasinferior hydrolytic stability and under humid and/or elevatedtemperature conditions, alkali metals could migrate out of the glassbody to the interface of the glass surface and coupling agent layer (ifpresent), or even migrate into the coupling agent layer, if present. Ifalkali metals migrate, as described above, and there is a change in pH,hydrolysis of Si—O—Si bonds at the glass/coupling agent layer interfaceor in the coupling agent layer itself may weaken either the couplingagent mechanical properties or its adhesion to the glass. Second, whenion-exchanged glasses are exposed to strong oxidant baths, such aspotassium nitrite baths, at elevated temperatures, such as 400° C. to450° C., and removed, organic chemical compositions on the surface ofthe glass are removed, making it particularly well suited for silanecoupling agents without further cleaning. For example, anon-ion-exchanged glass may have to be exposed to an additional surfacecleaning treatment, adding time and expense to the process.

In one exemplary embodiment, the coupling agent may comprise at leastone silane comprising an amine moiety and the polymer chemicalcomposition may comprise a polyimide chemical composition. Now referringto FIG. 32, without being bound by theory, it is believed that theinteraction between this amine moiety interaction and the polyamic acidprecursor of the polyimide follows a stepwise process. As shown in FIG.32, the first step is formation of a polyamic acid salt between acarboxyl moiety of the polyamic acid and the amine moiety. The secondstep is thermal conversion of the salt into an amide moiety. The thirdsstep is further conversion of the amide moiety into an imide moiety withscission of the polymer amide bonds. The result is a covalent imideattachment of a shortened polymer chain (polyimide chain) to an aminemoiety of the coupling agent, as shown in FIG. 32.

Referring collectively to FIGS. 7 and 8, FIG. 7 contains a process flowdiagram 500 of a method for producing a coated glass container 100having a low-friction coating and FIG. 8 schematically depicts theprocess described in the flow diagram. In a first step 502, glass tubestock 1000 formed from an ion-exchangeable glass composition isinitially shaped into glass containers 900 (specifically glass vials inthe embodiment depicted) using conventional shaping and formingtechniques. In step 504, the glass containers 900 are loaded into amagazine 604 using a mechanical magazine loader 602. The magazine loader602 may be a mechanical gripping device, such as a caliper or the like,which is capable of gripping multiple glass containers at one time.Alternatively, the gripping device may utilize a vacuum system to gripthe glass containers 900. The magazine loader 602 may be coupled to arobotic arm or other, similar device capable of positioning the magazineloader 602 with respect to the glass containers 900 and the magazine604.

In a next step 506, the magazine 604 loaded with glass containers 900 istransferred with a mechanical conveyor, such as a conveyor belt 606,overhead crane or the like, to a cassette loading area. Thereafter, instep 508, the magazine 604 is loaded into a cassette 608. The cassette608 is constructed to hold a plurality of magazines such that a largenumber of glass containers can be processed simultaneously. Eachmagazine 604 is positioned in the cassette 608 utilizing a cassetteloader 610. The cassette loader 610 may be a mechanical gripping device,such as a caliper or the like, which is capable of gripping one or moremagazines at a time. Alternatively, the gripping device may utilize avacuum system to grip the magazines 604. The cassette loader 610 may becoupled to a robotic arm or other, similar device capable of positioningthe cassette loader 610 with respect to the cassette 608 and themagazine 604.

In a next step 510, the cassette 608 containing the magazines 604 andglass containers 900 is transferred to an ion exchange station andloaded into an ion exchange tank 614 to facilitate chemicallystrengthening the glass containers 900. The cassette 608 is transferredto the ion exchange station with a cassette transfer device 612. Thecassette transfer device 612 may be a mechanical gripping device, suchas a caliper or the like, which is capable of gripping the cassette 608.Alternatively, the gripping device may utilize a vacuum system to gripthe cassette 608. The cassette transfer device 612 and attached cassette608 may be automatically conveyed from the cassette loading area to theion exchange station with an overhead rail system, such as a gantrycrane or the like. Alternatively, the cassette transfer device 612 andattached cassette 608 may be conveyed from the cassette loading area tothe ion exchange station with a robotic arm. In yet another embodiment,the cassette transfer device 612 and attached cassette 608 may beconveyed from the cassette loading area to the ion exchange station witha conveyor and, thereafter, transferred from the conveyor to the ionexchange tank 614 with a robotic arm or an overhead crane.

Once the cassette transfer device 612 and attached cassette are at theion exchange station, the cassette 608 and the glass containers 900contained therein may be preheated prior to immersing the cassette 608and the glass containers 900 in the ion exchange tank 614. The cassette608 may be preheated to a temperature greater than room temperature andless than or equal to the temperature of the molten salt bath in the ionexchange tank. For example, the glass containers may be preheated to atemperature from about 300° C.-500° C.

The ion exchange tank 614 contains a bath of molten salt 616, such as amolten alkali salt, such as KNO₃, NaNO₃ and/or combinations thereof. Inone embodiment, the bath of molten salt is 100% molten KNO₃ which ismaintained at a temperature greater than or equal to about 350° C. andless than or equal to about 500° C. However, it should be understoodthat baths of molten alkali salt having various other compositionsand/or temperatures may also be used to facilitate ion exchange of theglass containers.

In step 512, the glass containers 900 are ion exchange strengthened inthe ion exchange tank 614. Specifically, the glass containers areimmersed in the molten salt and held there for a period of timesufficient to achieve the desired compressive stress and depth of layerin the glass containers 900. For example, in one embodiment, the glasscontainers 900 may be held in the ion exchange tank 614 for a timeperiod sufficient to achieve a depth of layer of up to about 100 μm witha compressive stress of at least about 300 MPa or even 350 MPa. Theholding period may be less than 30 hours or even less than 20 hours.However it should be understood that the time period with which theglass containers are held in the tank 614 may vary depending on thecomposition of the glass container, the composition of the bath ofmolten salt 616, the temperature of the bath of molten salt 616, and thedesired depth of layer and the desired compressive stress.

After the glass containers 900 are ion exchange strengthened, thecassette 608 and glass containers 900 are removed from the ion exchangetank 614 using the cassette transfer device 612 in conjunction with arobotic arm or overhead crane. During removal from the ion exchange tank614, the cassette 608 and the glass containers 900 are suspended overthe ion exchange tank 614 and the cassette 608 is rotated about ahorizontal axis such that any molten salt remaining in the glasscontainers 900 is emptied back into the ion exchange tank 614.Thereafter, the cassette 608 is rotated back to its initial position andthe glass containers are allowed to cool prior to being rinsed.

The cassette 608 and glass containers 900 are then transferred to arinse station with the cassette transfer device 612. This transfer maybe performed with a robotic arm or overhead crane, as described above,or alternatively, with an automatic conveyor such as a conveyor belt orthe like. In a next step 514, the cassette 608 and glass containers 900are lowered into a rinse tank 618 containing a water bath 620 to removeany excess salt from the surfaces of the glass containers 900. Thecassette 608 and glass containers 900 may be lowered into the rinse tank618 with a robotic arm, overhead crane or similar device which couplesto the cassette transfer device 612. The cassette 608 and glasscontainers 900 are then withdrawn from the rinse tank 618, suspendedover the rinse tank 618, and the cassette 608 is rotated about ahorizontal axis such that any rinse water remaining in the glasscontainers 900 is emptied back into the rinse tank 618. In someembodiments, the rinsing operation may be performed multiple timesbefore the cassette 608 and glass containers 900 are moved to the nextprocessing station.

In one particular embodiment, the cassette 608 and the glass containers900 are dipped in a water bath at least twice. For example, the cassette608 may be dipped in a first water bath and, subsequently, a second,different water bath to ensure that all residual alkali salts areremoved from the surface of the glass article. The water from the firstwater bath may be sent to waste water treatment or to an evaporator.

In a next step 516, the magazines 604 are removed from the cassette 608with the cassette loader 610. Thereafter, in step 518, the glasscontainers 900 are unloaded from the magazine 604 with the magazineloader 602 and transferred to a washing station. In step 520, the glasscontainers are washed with a jet of de-ionized water 624 emitted from anozzle 622. The jet of de-ionized water 624 may be mixed with compressedair.

Optionally, in step 521 (not depicted in FIG. 8), the glass containers900 are transferred to an inspection station where the glass containersare inspected for flaws, debris, discoloration and the like.

In step 522, the glass containers 900 are transferred to the coatingstation with the magazine loader 602 where the low-friction coating isapplied to the glass containers 900. In some embodiments, theapplication of the low-friction coating may include the application of acoupling agent directly to the surface of the glass container and apolymer chemical composition on the coupling agent, as described above.In these embodiments, the glass containers 900 are partially immersed ina first dip tank 626 which contains the coupling agent 628 to coat theexterior surface of the glass containers with the coupling agent.Alternatively, the coupling agent may be spray applied. Thereafter, theglass containers are withdrawn from the first dip tank 626 and thecoupling agent is dried. In some embodiments, such as embodiments wherethe coupling agent comprises one or more silane chemical compositions asdescribed above, the glass containers 900 may be conveyed to an ovenwhere the glass containers 900 are dried at about 120° C. for 15minutes.

While the process schematically depicted in FIG. 8 includes a step ofcoating the outside of the glass containers with a coupling agent, itshould be understood that this step is only used for those coatingcompositions in which a coupling agent is needed. In other embodimentsof low-friction coatings in which a coupling agent is not needed, thestep of applying the coupling agent may be omitted.

Thereafter, the glass containers 900 are conveyed to the coating diptank 630 with the magazine loader 602. The coating dip tank 630 isfilled with the polymer chemical composition coating solution 632comprising a polymer chemical composition described herein above. Theglass containers are at least partially immersed in the polymer chemicalcomposition coating solution 632 to coat the polymer chemicalcomposition onto the glass containers, either directly onto the exteriorsurface of the glass containers 900 or onto the coupling agent which isalready coated on the glass containers 900. Thereafter, the polymerchemical composition solution is dried to remove any solvents. In oneembodiment, where the polymer chemical composition coating solutioncontains NOVASTRAT® 800 as described above, the coating solution may bedried by conveying the glass containers 900 to an oven and heating theglass containers at 150° C. for 20 minutes. Once the polymer chemicalcomposition coatings solution is dried, the glass containers 900 may(optionally) be re-dipped into the polymer chemical composition coatingdip tank 630 to apply one or more additional layers of polymer chemicalcomposition. In some embodiments, the polymer chemical compositioncoating is applied to the entire external surface of the container,while in other embodiments the low-friction coating is only applied to aportion of the external surface of the container. While the couplingagent and polymer chemical composition are described herein, in someembodiments, as being applied in two separate steps, it should beunderstood that in an alternative embodiment, the coupling agent andlow-friction coating are applied in a single step, such as when thecoupling agent and the polymer chemical composition are combined in amixture.

Once the polymer chemical composition coating solution 632 has beenapplied to the glass containers 900, the polymer chemical composition iscured on the glass containers 900. The curing process depends on thetype of polymer chemical composition coating applied to the coatingprocess and may include thermally curing the coating, curing the coatingwith UV light, and/or a combination thereof. In the embodimentsdescribed herein where the polymer chemical composition coatingcomprises a polyimide such as the polyimide formed by the NOVASTRAT® 800polyamic acid coating solution described above, the glass containers 900are conveyed to an oven 634 where they are heated from 150° C. toapproximately 350° C. over a period of about 5 to 30 minutes. Uponremoval of the glass containers from the oven, the polymer chemicalcomposition coating is cured thereby producing a coated glass containerwith a low-friction coating.

After the low-friction coating has been applied to the glass container,the coated glass containers 100 are transferred to a packaging processin step 524 where the containers are filled and/or to an additionalinspection station.

Various properties of the coated glass containers (i.e., coefficient offriction, horizontal compression strength, 4-point bend strength) may bemeasured when the coated glass containers are in an as-coated condition(i.e., following application of the coating without any additionaltreatments) or following one or more processing treatments, such asthose similar or identical to treatments performed on a pharmaceuticalfilling line, including, without limitation, washing, lyophilization,depyrogenation, autoclaving, or the like.

Depyrogenation is a process wherein pyrogens are removed from asubstance. Depyrogenation of glass articles, such as pharmaceuticalpackages, can be performed by a thermal treatment applied to a sample inwhich the sample is heated to an elevated temperature for a period oftime. For example, depyrogenation may include heating a glass containerto a temperature of between about 250° C. and about 380° C. for a timeperiod from about 30 seconds to about 72 hours, including, withoutlimitation, 20 minutes, 30 minutes 40 minutes, 1 hour, 2 hours, 4 hours,8 hours, 12 hours, 24 hours, 48 hours, and 72 hours. Following thethermal treatment, the glass container is cooled to room temperature.One conventional depyrogenation condition commonly employed in thepharmaceutical industry is thermal treatment at a temperature of about250° C. for about 30 minutes. However, it is contemplated that the timeof thermal treatment may be reduced if higher temperatures are utilized.The coated glass containers, as described herein, may be exposed toelevated temperatures for a period of time. The elevated temperaturesand time periods of heating described herein may or may not besufficient to depyrogenate a glass container. However, it should beunderstood that some of the temperatures and times of heating describedherein are sufficient to depyrogenate a coated glass container, such asthe coated glass containers described herein. For example, as describedherein, the coated glass containers may be exposed to temperatures ofabout 260° C., about 270° C., about 280° C., about 290° C., about 300°C., about 310° C., about 320° C., about 330° C., about 340° C., about350° C., about 360° C., about 370° C., about 380° C., about 390° C., orabout 400° C., for a period of time of 30 minutes.

As used herein, lyophilization conditions (i.e., freeze drying) refer toa process in which a sample is filled with a liquid that containsprotein and then frozen at −100° C., followed by water sublimation for20 hours at −15° C. under vacuum.

As used herein, autoclave conditions refer to steam purging a sample for10 minutes at 100° C., followed by a 20 minute dwelling period whereinthe sample is exposed to a 121° C. environment, followed by 30 minutesof heat treatment at 121° C.

The coefficient of friction (μ) of the portion of the coated glasscontainer with the low-friction coating may have a lower coefficient offriction than a surface of an uncoated glass container formed from asame glass composition. A coefficient of friction (μ) is a quantitativemeasurement of the friction between two surfaces and is a function ofthe mechanical and chemical properties of the first and second surfaces,including surface roughness, as well as environmental conditions suchas, but not limited to, temperature and humidity. As used herein, acoefficient of friction measurement for coated glass container 100 isreported as the coefficient of friction between the outer surface of afirst glass container (having an outer diameter of between about 16.00mm and about 17.00 mm) and the outer surface of second glass containerwhich is identical to the first glass container, wherein the first andsecond glass containers have the same body and the same coatingcomposition (when applied) and have been exposed to the sameenvironments prior to fabrication, during fabrication, and afterfabrication. Unless otherwise denoted herein, the coefficient offriction refers to the maximum coefficient of friction measured with anormal load of 30 N measured on a vial-on-vial testing jig, as describedherein. However, it should be understood that a coated glass containerwhich exhibits a maximum coefficient of friction at a specific appliedload will also exhibit the same or better (i.e., lower) maximumcoefficient of friction at a lesser load. For example, if a coated glasscontainer exhibits a maximum coefficient of friction of 0.5 or lowerunder an applied load of 50 N, the coated glass container will alsoexhibit a maximum coefficient of friction of 0.5 or lower under anapplied load of 25 N.

In the embodiments described herein, the coefficient of friction of theglass containers (both coated and uncoated) is measured with avial-on-vial testing jig. The testing jig 200 is schematically depictedin FIG. 9. The same apparatus may also be used to measure the frictiveforce between two glass containers positioned in the jig. Thevial-on-vial testing jig 200 comprises a first clamp 212 and a secondclamp 222 arranged in a cross configuration. The first clamp 212comprises a first securing arm 214 attached to a first base 216. Thefirst securing arm 214 attaches to the first glass container 210 andholds the first glass container 210 stationary relative to the firstclamp 212. Similarly, the second clamp 222 comprises a second securingarm 224 attached to a second base 226. The second securing arm 224attaches to the second glass container 220 and holds it stationaryrelative to the second clamp 222. The first glass container 210 ispositioned on the first clamp 212 and the second glass container 220 ispositioned of the second clamp 222 such that the long axis of the firstglass container 210 and the long axis of the second glass container 220are positioned at about a 90° angle relative to one another and on ahorizontal plane defined by the x-y axis.

A first glass container 210 is positioned in contact with the secondglass container 220 at a contact point 230. A normal force is applied ina direction orthogonal to the horizontal plane defined by the x-y axis.The normal force may be applied by a static weight or other forceapplied to the second clamp 222 upon a stationary first clamp 212. Forexample, a weight may be positioned on the second base 226 and the firstbase 216 may be placed on a stable surface, thus inducing a measurableforce between the first glass container 210 and the second glasscontainer 220 at the contact point 230. Alternatively, the force may beapplied with a mechanical apparatus, such as a UMT (universal mechanicaltester) machine.

The first clamp 212 or second clamp 222 may be moved relative to theother in a direction which is at a 45° angle with the long axis of thefirst glass container 210 and the second glass container 220. Forexample, the first clamp 212 may be held stationary and the second clamp222 may be moved such that the second glass container 220 moves acrossthe first glass container 210 in the direction of the x-axis. A similarsetup is described by R. L. De Rosa et al., in “Scratch ResistantPolyimide Coatings for Alumino Silicate Glass surfaces” in The Journalof Adhesion, 78: 113-127, 2002. To measure the coefficient of friction,the force required to move the second clamp 222 and the normal forceapplied to first and second glass containers 210,220 are measured withload cells and the coefficient of friction is calculated as the quotientof the frictive force and the normal force. The jig is operated in anenvironment of 25° C. and 50% relative humidity.

In the embodiments described herein, the portion of the coated glasscontainer with the low-friction coating has a coefficient of friction ofless than or equal to about 0.7 relative to a like-coated glasscontainer, as determined with the vial-on-vial jig described above. Inother embodiments, the coefficient of friction may be less than or equalto about 0.6, or even less than or equal to about 0.5. In someembodiments, the portion of the coated glass container with thelow-friction coating has a coefficient of friction of less than or equalto about 0.4 or even less than or equal to about 0.3. Coated glasscontainers with coefficients of friction less than or equal to about 0.7generally exhibit improved resistance to frictive damage and, as aresult, have improved mechanical properties. For example, conventionalglass containers (without a low-friction coating) may have a coefficientof friction of greater than 0.7.

In some embodiments described herein, the coefficient of friction of theportion of the coated glass container with the low-friction coating isat least 20% less than a coefficient of friction of a surface of anuncoated glass container formed from a same glass composition. Forexample, the coefficient of friction of the portion of the coated glasscontainer with the low-friction coating may be at least 20% less, atleast 25% less, at least 30% less, at least 40% less, or even at least50% less than a coefficient of friction of a surface of an uncoatedglass container formed from a same glass composition.

In some embodiments, the portion of the coated glass container with thelow-friction coating may have a coefficient of friction of less than orequal to about 0.7 after exposure to a temperature of about 260° C.,about 270° C., about 280° C., about 290° C., about 300° C., about 310°C., about 320° C., about 330° C., about 340° C., about 350° C., about360° C., about 370° C., about 380° C., about 390° C., or about 400° C.,for a period of time of 30 minutes. In other embodiments, the portion ofthe coated glass container with the low-friction coating may have acoefficient of friction of less than or equal to about 0.7, (i.e., lessthan or equal to about 0.6, less than or equal to about 0.5, less thanor equal to about 0.4, or even less than or equal to about 0.3) afterexposure to a temperature of about 260° C., about 270° C., about 280°C., about 290° C., about 300° C., about 310° C., about 320° C., about330° C., about 340° C., about 350° C., about 360° C., about 370° C.,about 380° C., about 390° C., or about 400° C., for a period of time of30 minutes. In some embodiments, the coefficient of friction of theportion of the coated glass container with the low-friction coating maynot increase by more than about 30% after exposure to a temperature ofabout 260° C. for 30 minutes. In other embodiments, coefficient offriction of the portion of the coated glass container with thelow-friction coating may not increase by more than about 30% (i.e.,about 25%, about 20%, about 15%, or event about 10%) after exposure to atemperature of about 260° C., about 270° C., about 280° C., about 290°C., about 300° C., about 310° C., about 320° C., about 330° C., about340° C., about 350° C., about 360° C., about 370° C., about 380° C.,about 390° C., or about 400° C., for a period of time of 30 minutes. Inother embodiments, coefficient of friction of the portion of the coatedglass container with the low-friction coating may not increase by morethan about 0.5 (i.e., about 0.45, about 0.04, about 0.35, about 0.3,about 0.25, about 0.2, about 0.15, about 0.1, or event about 0.5) afterexposure to a temperature of about 260° C., about 270° C., about 280°C., about 290° C., about 300° C., about 310° C., about 320° C., about330° C., about 340° C., about 350° C., about 360° C., about 370° C.,about 380° C., about 390° C., or about 400° C., for a period of time of30 minutes. In some embodiments, the coefficient of friction of theportion of the coated glass container with the low-friction coating maynot increase at all after exposure to a temperature of about 260° C.,about 270° C., about 280° C., about 290° C., about 300° C., about 310°C., about 320° C., about 330° C., about 340° C., about 350° C., about360° C., about 370° C., about 380° C., about 390° C., or about 400° C.,for a period of time of 30 minutes.

In some embodiments, the portion of the coated glass container with thelow-friction coating may have a coefficient of friction of less than orequal to about 0.7 after being submerged in a water bath at atemperature of about 70° C. for 10 minutes. In other embodiments, theportion of the coated glass container with the low-friction coating mayhave a coefficient of friction of less than or equal to about 0.7,(i.e., less than or equal to about 0.6, less than or equal to about 0.5,less than or equal to about 0.4, or even less than or equal to about0.3) after being submerged in a water bath at a temperature of about 70°C. for 5 minutes, 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50minutes, or even 1 hour. In some embodiments, the coefficient offriction of the portion of the coated glass container with thelow-friction coating may not increase by more than about 30% after beingsubmerged in a water bath at a temperature of about 70° C. for 10minutes. In other embodiments, coefficient of friction of the portion ofthe coated glass container with the low-friction coating may notincrease by more than about 30% (i.e., about 25%, about 20%, about 15%,or event about 10%) after being submerged in a water bath at atemperature of about 70° C. for 5 minutes, 10 minutes, 20 minutes, 30minutes, 40 minutes, 50 minutes, or even 1 hour. In some embodiments,the coefficient of friction of the portion of the coated glass containerwith the low-friction coating may not increase at all after beingsubmerged in a water bath at a temperature of about 70° C. for 5minutes, 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, oreven 1 hour.

In some embodiments, the portion of the coated glass container with thelow-friction coating may have a coefficient of friction of less than orequal to about 0.7 after exposure to lyophilization conditions. In otherembodiments, the portion of the coated glass container with thelow-friction coating may have a coefficient of friction of less than orequal to about 0.7, (i.e., less than or equal to about 0.6, less than orequal to about 0.5, less than or equal to about 0.4, or even less thanor equal to about 0.3) after exposure to lyophilization conditions. Insome embodiments, the coefficient of friction of the portion of thecoated glass container with the low-friction coating may not increase bymore than about 30% after exposure to lyophilization conditions. Inother embodiments, coefficient of friction of the portion of the coatedglass container with the low-friction coating may not increase by morethan about 30% (i.e., about 25%, about 20%, about 15%, or event about10%) after exposure to lyophilization conditions. In some embodiments,the coefficient of friction of the portion of the coated glass containerwith the low-friction coating may not increase at all after exposure tolyophilization conditions.

In some embodiments, the portion of the coated glass container with thelow-friction coating may have a coefficient of friction of less than orequal to about 0.7 after exposure to autoclave conditions. In otherembodiments, the portion of the coated glass container with thelow-friction coating may have a coefficient of friction of less than orequal to about 0.7, (i.e., less than or equal to about 0.6, less than orequal to about 0.5, less than or equal to about 0.4, or even less thanor equal to about 0.3) after exposure to autoclave conditions. In someembodiments, the coefficient of friction of the portion of the coatedglass container with the low-friction coating may not increase by morethan about 30% after exposure to autoclave conditions. In otherembodiments, coefficient of friction of the portion of the coated glasscontainer with the low-friction coating may not increase by more thanabout 30% (i.e., about 25%, about 20%, about 15%, or event about 10%)after exposure to autoclave conditions. In some embodiments, thecoefficient of friction of the portion of the coated glass containerwith the low-friction coating may not increase at all after exposure toautoclave conditions.

The coated glass containers described herein have a horizontalcompression strength. Referring to FIG. 1, the horizontal compressionstrength, as described herein, is measured by positioning the coatedglass container 100 horizontally between two parallel platens which areoriented in parallel to the long axis of the glass container. Amechanical load is then applied to the coated glass container 100 withthe platens in the direction perpendicular to the long axis of the glasscontainer. The load rate for vial compression is 0.5 in/min, meaningthat the platens move towards each other at a rate of 0.5 in/min. Thehorizontal compression strength is measured at 25° C. and 50% relativehumidity. A measurement of the horizontal compression strength can begiven as a failure probability at a selected normal compression load. Asused herein, failure occurs when the glass container ruptures under ahorizontal compression in least 50% of samples. In some embodiments, acoated glass container may have a horizontal compression strength atleast 10%, 20%, or 30% greater than an uncoated vial.

Referring now to FIGS. 1 and 9, the horizontal compression strengthmeasurement may also be performed on an abraded glass container.Specifically, operation of the testing jig 200 may create damage on thecoated glass container outer surface 122, such as a surface scratch orabrasion that weakens the strength of the coated glass container 100.The glass container is then subjected to the horizontal compressionprocedure described above, wherein the container is placed between twoplatens with the scratch pointing outward parallel to the platens. Thescratch can be characterized by the selected normal pressure applied bya vial-on-vial jig and the scratch length. Unless identified otherwise,scratches for abraded glass containers for the horizontal compressionprocedure are characterized by a scratch length of 20 mm created by anormal load of 30 N.

The coated glass containers can be evaluated for horizontal compressionstrength following a heat treatment. The heat treatment may be exposureto a temperature of about 260° C., about 270° C., about 280° C., about290° C., about 300° C., about 310° C., about 320° C., about 330° C.,about 340° C., about 350° C., about 360° C., about 370° C., about 380°C., about 390° C., or about 400° C., for a period of time of 30 minutes.In some embodiments, the horizontal compression strength of the coatedglass container is not reduced by more than about 20%, 30%, or even 40%after being exposed to a heat treatment, such as those described above,and then being abraded, as described above. In one embodiment, thehorizontal compression strength of the coated glass container is notreduced by more than about 20% after being exposed to a heat treatmentof about 260° C., about 270° C., about 280° C., about 290° C., about300° C., about 310° C., about 320° C., about 330° C., about 340° C.,about 350° C., about 360° C., about 370° C., about 380° C., about 390°C., or about 400° C., for a period of time of 30 minutes, and then beingabraded.

The coated glass articles described herein may be thermally stable afterheating to a temperature of at least 260° C. for a time period of 30minutes. The phrase “thermally stable,” as used herein, means that thelow friction coating applied to the glass article remains substantiallyintact on the surface of the glass article after exposure to theelevated temperatures such that, after exposure, the mechanicalproperties of the coated glass article, specifically the coefficient offriction and the horizontal compression strength, are only minimallyaffected, if at all. This indicates that the low friction coatingremains adhered to the surface of the glass following elevatedtemperature exposure and continues to protect the glass article frommechanical insults such as abrasions, impacts and the like.

In the embodiments described herein, a coated glass article isconsidered to be thermally stable if the coated glass article meets botha coefficient of friction standard and a horizontal compression strengthstandard after heating to the specified temperature and remaining atthat temperature for the specified time. To determine if the coefficientof friction standard is met, the coefficient of friction of a firstcoated glass article is determined in as-received condition (i.e., priorto any thermal exposure) using the testing jig depicted in FIG. 9 and a30 N applied load. A second coated glass article (i.e., a glass articlehaving the same glass composition and the same coating composition asthe first coated glass article) is thermally exposed under theprescribed conditions and cooled to room temperature. Thereafter, thecoefficient of friction of the second glass article is determined usingthe testing jig depicted in FIG. 9 to abrade the coated glass articlewith a 30 N applied load resulting in an abraded (i.e., a “scratch”)having a length of approximately 20 mm. If the coefficient of frictionof the second coated glass article is less than 0.7 and the surface ofthe glass of the second glass article in the abraded area does not haveany observable damage, then the coefficient of friction standard is metfor purposes of determining the thermal stability of the low frictioncoating. The term “observable damage,” as used herein means that thesurface of the glass in the abraded area of the glass article containsless than six glass checks per 0.5 cm of length of the abraded area whenobserved with a Nomarski or differential interference contrast (DIC)spectroscopy microscope at a magnification of 100× with LED or halogenlight sources. A standard definition of a glass check or glass checkingis described in G. D. Quinn, “NIST Recommended Practice Guide:Fractography of Ceramics and Glasses,” NIST special publication 960-17(2006).

To determine if the horizontal compression strength standard is met, afirst coated glass article is abraded in the testing jig depicted inFIG. 9 under a 30 N load to form a 20 mm scratch. The first coated glassarticle is then subjected to a horizontal compression test, as describedherein, and the retained strength of the first coated glass article isdetermined. A second coated glass article (i.e., a glass article havingthe same glass composition and the same coating composition as the firstcoated glass article) is thermally exposed under the prescribedconditions and cooled to room temperature. Thereafter, the second coatedglass article is abraded in the testing jig depicted in FIG. 9 under a30 N load. The second coated glass article is then subjected to ahorizontal compression test, as described herein, and the retainedstrength of the second coated glass article is determined. If theretained strength of the second coated glass article does not decreaseby more than about 20% relative to the first coated glass article thenthe horizontal compression strength standard is met for purposes ofdetermining the thermal stability of the low friction coating.

In the embodiments described herein, the coated glass containers areconsidered to be thermally stable if the coefficient of frictionstandard and the horizontal compression strength standard are met afterexposing the coated glass containers to a temperature of at least about260° C. for a time period of about 30 minutes (i.e., the coated glasscontainers are thermally stable at a temperature of at least about 260°C. for a time period of about 30 minutes). The thermal stability mayalso be assessed at temperatures from about 260° C. up to about 400° C.For example, in some embodiments, the coated glass containers will beconsidered to be thermally stable if the standards are met at atemperature of at least about 270° C. or even about 280° C. for a timeperiod of about 30 minutes. In still other embodiments, the coated glasscontainers will be considered to be thermally stable if the standardsare met at a temperature of at least about 290° C. or even about 300° C.for a time period of about 30 minutes. In further embodiments, thecoated glass containers will be considered to be thermally stable if thestandards are met at a temperature of at least about 310° C. or evenabout 320° C. for a time period of about 30 minutes. In still otherembodiments, the coated glass containers will be considered to bethermally stable if the standards are met at a temperature of at leastabout 330° C. or even about 340° C. for a time period of about 30minutes. In yet other embodiments, the coated glass containers will beconsidered to be thermally stable if the standards are met at atemperature of at least about 350° C. or even about 360° C. for a timeperiod of about 30 minutes. In some other embodiments, the coated glasscontainers will be considered to be thermally stable if the standardsare met at a temperature of at least about 370° C. or even about 380° C.for a time period of about 30 minutes. In still other embodiments, thecoated glass containers will be considered to be thermally stable if thestandards are met at a temperature of at least about 390° C. or evenabout 400° C. for a time period of about 30 minutes.

The coated glass containers disclosed herein may also be thermallystable over a range of temperatures, meaning that the coated glasscontainers are thermally stable by meeting the coefficient of frictionstandard and horizontal compression strength standard at eachtemperature in the range. For example, in the embodiments describedherein, the coated glass containers may be thermally stable from atleast about 260° C. to a temperature of less than or equal to about 400°C. In some embodiments, the coated glass containers may be thermallystable in a range from at least about 260° C. to about 350° C. In someother embodiments, the coated glass containers may be thermally stablefrom at least about 280° C. to a temperature of less than or equal toabout 350° C. In still other embodiments, the coated glass containersmay be thermally stable from at least about 290° C. to about 340° C. Inanother embodiment, the coated glass container may be thermally stableat a range of temperatures of about 300° C. to about 380° C. In anotherembodiment, the coated glass container may be thermally stable at arange of temperatures from about 320° C. to about 360° C.

The coated glass containers described herein have a four point bendstrength. To measure the four point bend strength of a glass container,a glass tube that is the precursor to the coated glass container 100 isutilized for the measurement. The glass tube has a diameter that is thesame as the glass container but does not include a glass container baseor a glass container mouth (i.e., prior to forming the tube into a glasscontainer). The glass tube is then subjected to a four point bend stresstest to induce mechanical failure. The test is performed at 50% relativehumidity with outer contact members spaced apart by 9″ and inner contactmembers spaced apart by 3″ at a loading rate of 10 mm/min.

The four point bend stress measurement may also be performed on a coatedand abraded tube. Operation of the testing jig 200 may create anabrasion on the tube surface such as a surface scratch that weakens thestrength of the tube, as described in the measurement of the horizontalcompression strength of an abraded vial. The glass tube is thensubjected to a four point bend stress test to induce mechanical failure.The test is performed at 25° C. and at 50% relative humidity using outerprobes spaced apart by 9″ and inner contact members spaced apart by 3″at a loading rate of 10 mm/min, while the tube is positioned such thatthe scratch is put under tension during the test.

In some embodiments, the four point bend strength of a glass tube with alow-friction coating after abrasion shows on average at least 10%, 20%,or even 50% higher mechanical strength than that for an uncoated glasstube abraded under the same conditions.

In some embodiments, after the coated glass container 100 is abraded byan identical glass container with a 30 N normal force, the coefficientof friction of the abraded area of the coated glass container 100 doesnot increase by more than about 20% during another abrasion by anidentical glass container with a 30 N normal force at the same spot, ordoes not increase at all. In other embodiments, after the coated glasscontainer 100 is abraded by an identical glass container with a 30 Nnormal force, the coefficient of friction of the abraded area of thecoated glass container 100 does not increase by more than about 15% oreven 10% during another abrasion by an identical glass container with a30 N normal force at the same spot, or does not increase at all.However, it is not necessary that all embodiments of the coated glasscontainer 100 display such properties.

Mass loss refers to a measurable property of the coated glass container100 which relates to the amount of volatiles liberated from the coatedglass container 100 when the coated glass container is exposed to aselected elevated temperature for a selected period of time. Mass lossis generally indicative of the mechanical degradation of the coating dueto thermal exposure. Since the glass body of the coated glass containerdoes not exhibit measureable mass loss at the temperatures reported, themass loss test, as described in detail herein, yields mass loss data foronly the low-friction coating that is applied to the glass container.Multiple factors may affect mass loss. For example, the amount oforganic material that can be removed from the coating may affect massloss. The breakdown of carbon backbones and side chains in a polymerwill result in a theoretical 100% removal of the coating. Organometallicpolymer materials typically lose their entire organic component, but theinorganic component remains behind. Thus, mass loss results arenormalized based upon how much of the coating is organic and inorganic(e.g., % silica of the coating) upon complete theoretical oxidation.

To determine the mass loss, a coated sample, such as a coated glassvial, is initially heated to 150° C. and held at this temperature for 30minutes to dry the coating, effectively driving off H₂O from thecoating. The sample is then heated from 150° C. to 350° C. at a ramprate of 10° C./min in an oxidizing environment, such as air. Forpurposes of mass loss determination, only the data collected from 150°C. to 350° C. is considered. In some embodiments, the low-frictioncoating has a mass loss of less than about 5% of its mass when heatedfrom a temperature of 150° C. to 350° C. at a ramp rate of about 10°C./minute. In other embodiments, the low-friction coating has a massloss of less than about 3% or even less than about 2% when heated from atemperature of 150° C. to 350° C. at a ramp rate of about 10° C./minute.In some other embodiments, the low-friction coating has a mass loss ofless than about 1.5% when heated from a temperature of 150° C. to 350°C. at a ramp rate of about 10° C./minute. In some other embodiments, thelow-friction coating loses substantially none of its mass when heatedfrom a temperature of 150° C. to 350° C. at a ramp rate of about 10°C./minute.

Mass loss results are based on a procedure wherein the weight of acoated glass container is compared before and after a heat treatment,such as a ramping temperature of 10°/minute from 150° C. to 350° C., asdescribed herein. The difference in weight between the pre-heattreatment and post-heat treatment vial is the weight loss of thecoating, which can be standardized as a percent weight loss of thecoating such that the pre-heat treatment weight of the coating (weightnot including the glass body of the container and following thepreliminary heating step) is known by comparing the weight on anuncoated glass container with a pre-treatment coated glass container.Alternatively, the total mass of coating may be determined by a totalorganic carbon test or other like means.

Outgassing refers to a measurable property of the coated glass container100 which relates to the amount of volatiles liberated from the coatedglass container 100 when the coated glass container is exposed to aselected elevated temperature for a selected period of time. Outgassingmeasurements are reported herein as an amount by weight of volatilesliberated per the surface area of the glass container having the coatingduring exposure to the elevated temperature for a time period. Since theglass body of the coated glass container does not exhibit measureableoutgassing at the temperatures reported for outgassing, the outgassingtest, as described in detail below, yields outgassing data forsubstantially only the low-friction coating that is applied to the glasscontainer. Outgassing results are based on a procedure wherein a coatedglass container 100 is placed in a glass sample chamber 402 of theapparatus 400 depicted in FIG. 10. A background sample of the emptysample chamber is collected prior to each sample run. The sample chamberis held under a constant 100 ml/min air purge as measured by rotometer406 while the furnace 404 is heated to 350° C. and held at thattemperature for 1 hour to collect the chamber background sample.Thereafter, the coated glass container 100 is positioned in the samplechamber 402 and the sample chamber 402 is held under a constant 100ml/min air purge and heated to an elevated temperature and held attemperature for a period of time to collect a sample from a coated glasscontainer 100. The glass sample chamber is made of Pyrex, limiting themaximum temperature of the analysis to 600° C. A Carbotrap 300 adsorbenttrap 408 is assembled on the exhaust port of the sample chamber toadsorb the resulting volatile species as they are released from thesample and are swept over the absorbent resin by the air purge gas 410where the volatile species are adsorbed. The absorbent resin is thenplaced directly into a Gerstel Thermal Desorption unit coupled directlyto a Hewlett Packard 5890 Series II gas chromatograph/Hewlett Packard5989 MS engine. Outgassing species are thermally desorbed at 350° C.from the adsorbent resin and cryogenically focused at the head of anon-polar gas chromatographic column (DB-5MS). The temperature withinthe gas chromatograph is increased at a rate of 10° C./min to a finaltemperature of 325° C., so as to provide for the separation andpurification of volatile and semi-volatile organic species. Themechanism of separation has been demonstrated to be based on the heatsof vaporization of different organic species resulting in, essentially,a boiling point or distillation chromatogram. Following separation,purified species are analyzed by traditional electron impact ionizationmass spectrometric protocols. By operating under standardizedconditions, the resulting mass spectra may be compared with existingmass spectral libraries.

In some embodiments, the coated glass containers described hereinexhibit an outgassing of less than or equal to 54.6 ng/cm², less than orequal to 27.3 ng/cm², or even less than or equal to 5.5 ng/cm² duringexposure to elevated temperature of 250° C., 275° C., 300° C., 320° C.,360° C., or even 400° C. for time periods of 15 minutes, 30 minutes, 45minutes, or 1 hour. Furthermore, the coated glass containers may bethermally stable in a specified range of temperatures, meaning that thecoated containers exhibit a certain outgassing, as described above, atevery temperature within the specified range. Prior to outgassingmeasurements, the coated glass containers may be in as-coated condition(i.e., immediately following application of the low-friction coating) orfollowing any one of depyrogenation, lyophilization, or autoclaving. Insome embodiments, the coated glass container 100 may exhibitsubstantially no outgassing.

In some embodiments, outgassing data may be used to determine mass lossof the low-friction coating. A pre-heat treatment coating mass can bedetermined by the thickness of the coating (determined by SEM image orother manner), the density of low-friction coating, and the surface areaof the coating. Thereafter, the coated glass container can be subjectedto the outgassing procedure, and mass loss can be determined by findingthe ratio of the mass expelled in outgassing to the pre-heat treatmentmass.

Referring to FIG. 11, the transparency and color of the coated containermay be assessed by measuring the light transmission of the containerwithin a range of wavelengths between 400-700 nm using aspectrophotometer. The measurements are performed such that a light beamis directed normal to the container wall such that the beam passesthrough the low-friction coating twice, first when entering thecontainer and then when exiting it. In some embodiments, the lighttransmission through the coated glass container may be greater than orequal to about 55% of a light transmission through an uncoated glasscontainer for wavelengths from about 400 nm to about 700 nm. Asdescribed herein, a light transmission can be measured before a thermaltreatment or after a thermal treatment, such as the heat treatmentsdescribed herein. For example, for each wavelength of from about 400 nmto about 700 nm, the light transmission may be greater than or equal toabout 55% of a light transmission through an uncoated glass container.In other embodiments, the light transmission through the coated glasscontainer is greater than or equal to about 55%, about 60%, about 65%,about 70%, about 75%, about 80%, or even about 90% of a lighttransmission through an uncoated glass container for wavelengths fromabout 400 nm to about 700 nm.

As described herein, a light transmission can be measured before anenvironmental treatment, such as a thermal treatment described herein,or after an environmental treatment. For example, following a heattreatment of about 260° C., about 270° C., about 280° C., about 290° C.,about 300° C., about 310° C., about 320° C., about 330° C., about 340°C., about 350° C., about 360° C., about 370° C., about 380° C., about390° C., or about 400° C., for a period of time of 30 minutes, or afterexposure to lyophilization conditions, or after exposure to autoclaveconditions, the light transmission through the coated glass container isgreater than or equal to about 55%, about 60%, about 65%, about 70%,about 75%, about 80%, or even about 90% of a light transmission throughan uncoated glass container for wavelengths from about 400 nm to about700 nm

In some embodiments, the coated glass container 100 may be perceived ascolorless and transparent to the naked human eye when viewed at anyangle. In some other embodiments, the low-friction coating 120 may havea perceptible tint, such as when the low-friction coating 120 comprisesa polyimide formed from poly(pyromelliticdianhydride-co-4,4′-oxydianiline) amic acid commercially available fromAldrich.

In some embodiments, the coated glass container 100 may have alow-friction coating 120 that is capable of receiving an adhesive label.That is, the coated glass container 100 may receive an adhesive label onthe coated surface such that the adhesive label is securely attached.However, the ability of attachment of an adhesive label is not arequirement for all embodiments of the coated glass containers 100described herein.

Particle Reduction and Contamination in Pharmaceutical Containers

Moreover, the coated glass containers described above also reduceparticle generation caused when pharmaceutical containers undergoprocessing.

As used herein, “processing” may encompass various steps for thepharmaceutical container after glass container production, wherein glasscontainer production may involve glass melting, ion exchangestrengthening, and glass coating. While many “processing” steps arecontemplated under this definition, “processing” may encompass, forexample, and not by way of limitation: 1) pharmaceutical filling lineprocedures, such as washing, conveying, singulating, aligning,depyrogenation, filling, stoppering and capping operations; 2) otherthermal treatment procedures, such as lyophilization and autoclaving;and 3) the shipping and handling of the pharmaceutical containerswhether filled or unfilled. In embodiments discussed below, “processing”involves the non-breakage inducing glass contact of pharmaceuticalcontainers in pharmaceutical filling lines.

As used herein, “non-breakage inducing glass contact” involvesinteractions with glass containers or impact upon glass containersduring processing which may cause unacceptable glass particle formationin conventional uncoated glass containers. Further, “non-breakageinducing glass contact” does not encompass glass interactions that causea breakage event wherein one or more glass containers may crack orshatter. For example and not by way of limitation, “non-breakageinducing glass contact” involves glass interaction or impact with manycontemplated objects, for example, glass to glass contact, or glass tometal contact. Additionally as described further below, “non-breakageinducing glass contact” may include impact on the glass container atvarious glass impact speeds and glass impact load forces. Whilenon-breakage inducing glass contact can result in particulate generationwithout causing complete container breakage, it is understood thatcomplete container breakage can also lead to generation of particulatesin all size ranges.

The pharmaceutical filling line embodiments described as followsillustrate the particle reduction properties of the coated glasscontainers. As stated above, conventional bulk pharmaceutical fillinglines for parenteral containers may comprise, but are not limited to,the steps of washing, conveying, singulating, aligning, depyrogenation,filling, stoppering and capping operations contained in a clean andsterile environment. The environmental control is designed to preventvisible and sub-visible particles from contaminating the drug product orcontainer. As used herein, particles having a size (e.g., a diameter)larger than 50 μm are “visible” particles, while particles having a sizeof 50 μm or below are “sub-visible” particles that are difficult to seewith the naked eye. Particles less than 10 μm which may find their wayinto the product solution are especially a concern for proteins orbiologic products; whereas, particles between 10 and 50 μm must bemonitored by all pharmaceutical manufacturers.

Isolator or barrier technology is commonly adopted to provide thehighest levels of sterility assurance. Inside an isolator or cleanroom,containers are conveyed between the operations using methods that allowand rely on systematic contact between containers. These conveyancemethods may include but are more not limited to mass containerconveyors, in line conveyors, star-wheel singulators, and the like.Moreover, although filling line designs vary, conveyance methods duringhandling can be classified into either bulk (wide belts or tables thatare commonly used during loading, depyrogenation and accumulation) orsingulated (single-file processing which is typically used for washing,filling and inspection). The container interactions may vary based onthe conveyance method.

For bulk handling, containers are conveyed by motion of a belt or tableunderneath the containers. Forces or pressure is applied to the mass ofcontainers as they are constrained by stationary barriers that guidevials relative to the movement of the conveyor drive system (e.g., belt,wheels, chains, etc). Lateral loads on the containers are generallyproportional to the number of containers between a stationary guide. Forthese operations, the interaction speed between adjacent containers isgenerally low; however, forces generated can be relatively large due tothe large collective mass of containers or pinch points along theconveyor system. As shown in FIG. 57, frictive sliding between vials mayoccur during bulk handling, which results in surface stress at thelocation of contact. When the surface stress exceeds the local materialstrength, the glass may partially fracture and generate particles. Asshown in the rotary accumulator table 700 depicted in FIG. 57, vialsmove 100 in the direction illustrated by the arrow; however, many of thevials 100 are constrained by inner guide 705 of the rotary accumulatortable 700. As moving vials slide past constrained vials adjacent theinner guide, frictive contact between vials results.

Containers in singulated conveyance are also transported by underneathconveyers. Although containers are more constrained than in bulk,containers (e.g., vials) can also slide and tilt resulting in frictivecontact between containers. Starwheels or screw feeders are often usedto transition between bulk and singulated conveyance modes. Referring toFIG. 58, these operations accelerate containers upon exit, often into oronto stationary containers or a mass of containers in bulk.Specifically, as shown in FIG. 58, the screw feeder 750 acceleratesvials 100 into vials located in a stationary plate 760 receivinglocation. Alternatively, equipment misalignment can also result inunintended container impact events. In these situations, container glassto glass contact is the primary impact event.

To quantify typical and maximum loads applied on containers, forcesbetween containers on multiple filling lines were probed using a piezosensor-based device (Tekscan® Flexiforce Load/Force Sensor) that recordsforces using a thin sensor. The sensor was inserted between containersduring typical operation on the accumulator table and other accessibleregions where impacts occur. Peak forces as high as 30 N were observedbetween containers, and typical frequent loads on these filling linesranged from approximately 2 to 10 N.

Bulk or high speed filling line handling methods for loading, conveyanceand singulation require part to part contact by design. The glasscontact between uncoated containers results in damage and airborneparticle generation. This is due in part to the high coefficient offriction of approximately 0.9 or more and the fact that glass is abrittle material that fractures under strain.

The coated glass containers described herein address this particlegeneration concern when the coated glass containers are processed.Specifically, because the present coated glass containers comprise achemically-strengthened glass container with a thermally stable, low-COFexterior coating, the described coated containers are able to withstandhigher stress on the filling line and are resistant to damage. Thestrengthening of the coated glass container also reduces the probabilityof catastrophic failure or breakage events from high stress loading, asecondary source of particles in both visible and sub-visiblecategories.

In one or more embodiments, the pharmaceutical container is provided asa glass body comprising glass and a coating bonded to at least a portionof the first surface of the glass body. In one embodiment, the glass ischemically strengthened by ion exchange. In further embodiments, thecoating comprises a polymer chemical composition and optionally acoupling agent as described above. In specific embodiments, the coatinghas sufficient thermal stability and coefficient of friction towithstand processing, for example, the processing steps conducting inthe pharmaceutical filling lines.

In other embodiments, the coated glass container demonstrates at least a50% reduction in average particle count for generated sub-visible glassparticles compared to an average particle count of generated sub-visibleglass particles by the processing of an uncoated glass container, whichhas the same shape and dimensions as the coated glass container. In oneembodiment, coated glass container is an uncoated borosilicate glasscontainer. In many of the embodiments herein, the particle amount mayrefer to the average particle count computed across multiple articlesamples. While various counting methods are contemplated, the averageparticle count is performed herein using the light obscuration techniquedescribed in United States Pharmacopoeia Reference Standard 788. In oneor more additional embodiments, the coated glass article may demonstratea reduction in average particle count of at least 75% compared to theaverage particle count for the uncoated glass article, or a reduction inaverage particle count of at least 90% compared to the average particlecount for the uncoated glass article, or a reduction in average particlecount of at least 99% compared to the average particle count for theuncoated glass article.

In one or more embodiments, the coated glass containers reduce formationof visible glass particles when subjected to the conditions associatedwith pharmaceutical filling lines or other types of processing. Theseconditions may include horizontal compression forces ranging from 0.1 Nto 30 N and glass to glass contact scratch velocities ranging from atleast 6 to 120 mm/min. Moreover, the coated glass containers results inthe amount of sub-visible glass particles at levels significantly belowthe maximum allowable levels defined by USP <788> i.e., the coated glasscontainer may produce a significant reduction in particles above andbeyond what is required by USP standards.

In further embodiments which demonstrate the improved particlereduction, the average particle count for sub-visible glass particleswith a size of 25 to 50 μm is from 0.1 to 1.0 when a coated glassarticle having a container volume of 3 mL undergoes processing, forexample, filling and the other steps defined above. In furtherembodiments, the average particle count for sub-visible glass particleswith a size of 25 to 50 μm may be from 0.1 to 1.5, or 0.1 to 2.5 whenthe coated glass article having a container volume of 3 mL undergoesfilling. In yet another coated glass article embodiment, the averageparticle count for sub-visible glass particles with a size of 10 to 25μm is from 1 to 20 when a coated glass article having a container volumeof 3 mL undergoes processing. Furthermore, the average particle countfor sub-visible glass particles with a size of 10 to 25 μm may be from 1to 15 when the coated glass article having a container volume of 3 mLundergoes processing.

While this present description focuses on vial filling lines, particlegeneration due to glass contact is also relevant to other containers anddelivery vehicles, such as cartridges, barrels, and syringes. Moreover,while many of the example vials described are 3 mL containers, thecoated glass containers of the present disclosure also encompassadditional vial sizes, ranging from 0.1 mL to 100 mL sizes.

As further illustrated in the Examples which follow, the coated glassarticles provide substantial reductions in particles in both the fillingenvironment (via real time particle monitors and collection) and inliquid drug product (via light obscuration) in two separate filling linestudies. Additionally, while many of the Examples demonstrate theimproved results of the coated glass vials of the present disclosure incontrast to uncoated glass containers, Example 25 below demonstrates theimproved results of the present coated glass containers relative toother conventional coated containers, such as silicone coatedborosilicate glass containers (See FIGS. 54 and 55).

EXAMPLES

The various embodiments of glass containers with low-friction coatingswill be further clarified by the following examples. The examples areillustrative in nature, and should not be understood to limit thesubject matter of the present disclosure.

Example 1

Glass vials were formed from Schott Type 1B glass and the glasscomposition identified as “Example E” of Table 1 of U.S. Pat. No.8,551,898 and entitled “Glass Compositions with Improved Chemical andMechanical Durability” assigned to Corning, Incorporated (hereinafter“the Reference Glass Composition”). The vials were washed with deionizedwater, blown dry with nitrogen, and dip coated with a 0.1% solution ofAPS (aminopropylsilsesquioxane). The APS coating was dried at 100° C. ina convection oven for 15 minutes. The vials were then dipped into a 0.1%solution of NOVASTRAT® 800 polyamic acid in a 15/85 toluene/DMF solutionor in a 0.1% to 1% poly(pyromellitic dianhydride-co-4,4′-oxydianiline)amic acid solution (Kapton precursor) in N-Methyl-2-pyrrolidone (NMP).The coated vials were heated to 150° C. and held for 20 minutes toevaporate the solvents. Thereafter, the coatings were cured by placingthe coated vials into a preheated furnace at 300° C. for 30 minutes.After curing, the vials coated with the 0.1% solution of NOVASTRAT® 800had no visible color. However, the vials coated with the solution ofpoly(pyromellitic dianhydride-co-4,4′oxydianiline) were visibly yellowin color. Both coatings exhibited a low coefficient of friction invial-to-vial contact tests.

Example 2

Glass vials formed from Schott Type 1B glass vials (asreceived/uncoated) and vials coated with a low-friction coating werecompared to assess the loss of mechanical strength due to abrasion. Thecoated vials were produced by first ion exchange strengthening glassvials produced from the Reference Glass Composition. The ion exchangestrengthening was performed in a 100% KNO₃ bath at 450° C. for 8 hours.Thereafter, the vials were washed with deionized water, blown dry withnitrogen, and dip coated with a 0.1% solution of APS(aminopropylsilsesquioxane). The APS coating was dried at 100° C. in aconvection oven for 15 minutes. The vials were then dipped into a 0.1%solution of NOVASTRAT® 800 polyamic acid in a 15/85 toluene/DMFsolution. The coated vials were heated to 150° C. and held for 20minutes to evaporate the solvents. Thereafter, the coatings were curedby placing the coated vials into a preheated furnace at 300° C. for 30minutes. The coated vials were then soaked in 70° C. de-ionized waterfor 1 hour and heated in air at 320° C. for 2 hours to simulate actualprocessing conditions.

Unabraded vials formed from the Schott Type 1B glass and unabraded vialsformed from the ion-exchange strengthened and coated Reference GlassComposition were tested to failure in a horizontal compression test(i.e., a plate was placed over the top of the vial and a plate wasplaced under the bottom of the vial and the plates were pressed togetherand the applied load at failure was determined with a load cell). FIG.12 graphically depicts the failure probability as a function of appliedload in a horizontal compression test for vials formed from a ReferenceGlass Composition, vials formed from a Reference Glass Composition in acoated and abraded condition, vials formed from Schott Type 1B glass,and vials formed from Schott Type 1B glass in an abraded condition. Thefailure loads of the unabraded vials are graphically depicted in theWeibull plots. Sample vials formed from the Schott Type 1B glass andunabraded vials formed from the ion-exchange strengthened and coatedglass were then placed in the vial-on-vial jig of FIG. 9 to abrade thevials and determine the coefficient of friction between the vials asthey were rubbed together over a contact area having a 0.3 mm diameter.The load on the vials during the test was applied with a UMT machine andwas varied between 24 N and 44 N. The applied loads and thecorresponding maximum coefficient of friction are reported in the Tablecontained in FIG. 13. For the uncoated vials, the maximum coefficient offriction varied from 0.54 to 0.71 (shown in FIG. 13 as vial samples“3&4” and “7&8”, respectively) and while for the coated vials themaximum coefficient of friction varied from 0.19 to 0.41 (shown in FIG.13 as vial samples “15&16” and “12&14”, respectively). Thereafter, thescratched vials were tested in the horizontal compression test to assessthe loss of mechanical strength relative to the unabraded vials. Thefailure loads applied to the unabraded vials are graphically depicted inthe Weibull plots of FIG. 12.

As shown in FIG. 12, the uncoated vials had a significant decrease instrength after abrasion whereas the coated vials had a relatively minordecrease in strength after abrasion. Based on these results, it isbelieved that the coefficient of friction between the vials should beless than 0.7 or 0.5, or even less than 0.45 in order to mitigate theloss of strength following vial-on-vial abrasion.

Example 3

In this example, multiple sets of glass tubes were tested in four pointbending to assess their respective strengths. A first set of tubesformed from the Reference Glass Composition was tested in four pointbending in as received condition (un-coated, non-ion exchangestrengthened). A second set of tubes formed from the Reference GlassComposition was tested in four point bending after being ion exchangestrengthened in a 100% KNO₃ bath at 450° C. for 8 hours. A third set oftubes formed from the Reference Glass Composition was tested in fourpoint bending after being ion exchange strengthened in a 100% KNO₃ bathat 450° C. for 8 hours and coated with 0.1% APS/0.1% NOVASTRAT® 800 asdescribed in Example 2. The coated tubes were also soaked in 70° C.de-ionized water for 1 hour and heated in air at 320° C. for 2 hours tosimulate actual processing conditions. These coated tubes were alsoabraded in the vial-on-vial jig shown in FIG. 9 under a 30 N load priorto bend testing. A fourth set of tubes formed from the Reference GlassComposition was tested in four point bending after being ion exchangestrengthened in a 100% KNO₃ bath at 450° C. for 1 hour. These uncoated,ion exchange strengthened tubes were also abraded in the vial-on-vialjig shown in FIG. 9 under a 30 N load prior to bend testing. A fifth setof tubes formed from Schott Type 1B glass was tested in four pointbending in as received condition (uncoated, non-ion exchangestrengthened). A sixth set of tubes formed from Schott Type 1B glass wastested in four point bending after being ion exchange strengthened in a100% KNO₃ bath at 450° C. for 1 hour. The results of testing aregraphically depicted in the Weibull plots displayed in FIG. 14.

Referring to FIG. 14, the second set of tubes which were non-abraded andformed from the Reference Glass Composition and ion exchangestrengthened withstood the highest stress before breaking. The third setof tubes which were coated with the 0.1% APS/0.1% NOVASTRAT® 800 priorto abrading showed a slight reduction in strength relative to theiruncoated, non-abraded equivalents (i.e., the second set of tubes).However, the reduction in strength was relatively minor despite beingsubjected to abrading after coating.

Example 4

Two sets of vials were prepared and run through a pharmaceutical fillingline. A pressure sensitive tape (commercially available from FujiFilm)was inserted in between the vials to measure contact/impact forcesbetween the vials and between the vials and the equipment. The first setof vials was formed from the Reference Glass Composition and was notcoated. The second set of vials was formed from the Reference GlassComposition and was coated with a low-friction polyimide based coatinghaving a coefficient of friction of about 0.25, as described above. Thepressure sensitive tapes were analyzed after the vials were run throughthe pharmaceutical filling line and demonstrated that the coated vialsof the second set exhibited a 2-3 times reduction in stress compared tothe un-coated vials of the first set.

Example 5

Three sets of four vials each were prepared. All the vials were formedfrom the Reference Glass Composition. The first set of vials was coatedwith the APS/NOVASTRAT® 800 coating as described in Example 2. Thesecond set of vials was dip coated with 0.1% DC806A in toluene. Thesolvent was evaporated at 50° C. and the coating was cured at 300° C.for 30 min. Each set of vials was placed in a tube and heated to 320° C.for 2.5 hours under an air purge to remove trace contaminants adsorbedinto the vials in the lab environment. Each set of samples was thenheated in the tube for another 30 minutes and the outgassed volatileswere captured on an activated carbon sorbent trap. The trap was heatedto 350° C. over 30 minutes to desorb any captured material which was fedinto a gas chromatograph-mass spectrometer. FIG. 15 depicts gaschromatograph-mass spectrometer output data for the APS/NOVASTRAT® 800coating. FIG. 16 depicts gas chromatography-mass spectrometer outputdata for the DC806A coating. No outgassing was detected from the 0.1%APS/0.1% NOVASTRAT® 800 coating or the DC806A coating.

A set of four vials was coated with a tie-layer using 0.5%/0.5%GAPS/APhTMS solution in methanol/water mixture. Each vial had a coatedsurface area of about 18.3 cm². Solvent was allowed to evaporate at 120°C. for 15 min from the coated vials. Then a 0.5% NOVASTRAT® 800solutions in dimethylacetamide was applied onto the samples. The solventwas evaporated at 150° C. for 20 min. These uncured vials were subjectedto an outgassing test described above. The vials were heated to 320° C.in a stream of air (100 mL/min) and upon reaching 320° C. the outgassedvolatiles were captured on an activated carbon sorbent traps every 15min. The traps then were heated to 350° C. over 30 minutes to desorb anycaptured material which was fed into a gas chromatograph-massspectrometer. Table 1 shows the amount of captured materials over thesegments of time that the samples were held at 320° C. Time zerocorresponds with the time that the sample first reached a temperature of320° C. As seen in Table 1, after 30 min of heating the amount ofvolatiles decreases below the instrument detection limit of 100 ng.Table 1 also reports the volatiles lost per square cm of coated surface.

TABLE 1 Table 1. Volatiles per vial and per area. Amount, Amount TimePeriod at 320° C. ng/vial ng/cm² 25° C. to 320° C. ramp (t = 0) 604043301 t = 0 to 15 min 9371 512 t = 15 to 30 min 321 18 t = 30 to 45 min<100 <5 t = 45 to 60 min <100 <5 t = 60 to 90 min <100 <5

Example 6

A plurality of vials was prepared with various coatings based on siliconresin or polyimides with and without coupling agents. When couplingagents were used, the coupling agents included APS and GAPS(3-aminopropyltrialkoxysilane), which is a precursor for APS. The outercoating layer was prepared from NOVASTRAT® 800, the poly(pyromelliticdianhydride-co-4,4′oxydianiline) described above, or silicone resinssuch as DC806A and DC255. The APS/Kapton coatings were prepared using a0.1% solution of APS (aminopropylsilsesquioxane) and 0.1% solution, 0.5%solution or 1.0% solutions of poly(pyromelliticdianhydride-co-4,4′-oxydianiline) amic acid (Kapton precursor) inN-methyl-2-pyrrolidone (NMP). Kapton coatings were also applied withouta coupling agent using a 1.0% solution of the poly(pyromelliticdianhydride-co-4,4′oxydianiline) in NMP. The APS/NOVASTRAT® 800 coatingswere prepared using a 0.1% solution of APS (aminopropylsilsesquioxane)and a 0.1% solution of NOVASTRAT® 800 polyamic acid in a 15/85toluene/DMF solution. The DC255 coatings were applied directly to theglass without a coupling agent using a 1.0% solution of DC255 inToluene. The APS/DC806A coatings were prepared by first applying a 0.1%solution of APS in water and then a 0.1% solution or a 0.5% solution ofDC806A in toluene. The GAPS/DC806A coatings were applied using a 1.0%solution of GAPS in 95 wt. % ethanol in water as a coupling agent andthen a 1.0% solution of DC806A in toluene. The coupling agents andcoatings were applied using dip coating methods as described herein withthe coupling agents being heat treated after application and the siliconresin and polyimide coatings being dried and cured after application.The coating thicknesses were estimated based on the concentrations ofthe solutions used. The Table contained in FIG. 17 lists the variouscoating compositions, estimated coating thicknesses and testingconditions.

Thereafter, some of the vials were tumbled to simulate coating damageand others were subjected to abrasion under 30 N and 50 N loads in thevial-on-vial jig depicted in FIG. 9. Thereafter, all the vials weresubjected to a lyophilization (freeze drying process) in which the vialswere filled with 0.5 mL of sodium chloride solution and then frozen at−100° C. Lyophilization was then performed for 20 hours at −15° C. undervacuum. The vials were inspected with optical quality assuranceequipment and under microscope. No damage to the coatings was observeddue to lyophilization.

Example 7

Three sets of six vials were prepared to assess the effect of increasingload on the coefficient of friction for uncoated vials and vials coatedwith Dow Corning DC 255 silicone resin. A first set of vials was formedfrom Type 1B glass and left uncoated. The second set of vials was formedfrom the Reference Glass Composition and coated with a 1% solution ofDC255 in Toluene and cured at 300° C. for 30 min. The third set of vialswas formed from Schott Type 1B glass and coated with a 1% solution ofDC255 in Toluene. The vials of each set were placed in the vial-on-vialjig depicted in FIG. 9 and the coefficient of friction relative to asimilarly coated vial was measured during abrasion under static loads of10 N, 30 N, and 50 N. The results are graphically reported in FIG. 18.As shown in FIG. 18, coated vials showed appreciably lower coefficientsof friction compared to uncoated vials when abraded under the sameconditions irrespective of the glass composition.

Example 8

Three sets of two glass vials were prepared with an APS/Kapton coating.First, each of the vials was dip coated in a 0.1% solution of APS(aminopropylsilsesquioxane). The APS coating was dried at 100° C. in aconvection oven for 15 minutes. The vials were then dipped into a 0.1%poly(pyromellitic dianhydride-co-4,4′-oxydianiline) amic acid solution(Kapton precursor) in N-methyl-2-pyrrolidone (NMP). Thereafter, thecoatings were cured by placing the coated vials into a preheated furnaceat 300° C. for 30 minutes.

Two vials were placed in the vial-on-vial jig depicted in FIG. 9 andabraded under a 10 N loaded. The abrasion procedure was repeated 4 moretimes over the same area and the coefficient of friction was determinedfor each abrasion. The vials were wiped between abrasions and thestarting point of each abrasion was positioned on a previouslynon-abraded area. However, each abrasion traveled over the same “track”.The same procedure was repeated for loads of 30 N and 50 N. Thecoefficients of friction of each abrasion (i.e., A1-A5) are graphicallydepicted in FIG. 19 for each load. As shown in FIG. 19, the coefficientof friction of the APS/Kapton coated vials was generally less than 0.30for all abrasions at all loads. The examples demonstrate improvedresistance to abrasion for polyimide coating when applied over a glasssurface treated with a coupling agent.

Example 9

Three sets of two glass vials were prepared with an APS coating. Each ofthe vials were dip coated in a 0.1% solution of APS(aminopropylsilsesquioxane) and heated at 100° C. in a convection ovenfor 15 minutes. Two vials were placed in the vial-on-vial jig depictedin FIG. 9 and abraded under a 10 N load. The abrasion procedure wasrepeated 4 more times over the same area and the coefficient of frictionwas determined for each abrasion. The vials were wiped between abrasionsand the starting point of each abrasion was positioned on a previouslynon-abraded area. However, each abrasion traveled over the same “track”.The same procedure was repeated for loads of 30 N and 50 N. Thecoefficients of friction of each abrasion (i.e., A1-A5) are graphicallydepicted in FIG. 20 for each load. As shown in FIG. 20, the coefficientof friction of the APS only coated vials is generally higher than 0.3and often reached 0.6 or even higher.

Example 10

Three sets of two glass vials were prepared with an APS/Kapton coating.Each of the vials was dip coated in a 0.1% solution of APS(aminopropylsilsesquioxane). The APS coating was heated at 100° C. in aconvection oven for 15 minutes. The vials were then dipped into a 0.1%poly(pyromellitic dianhydride-co-4,4′-oxydianiline) amic acid solution(Kapton precursor) in N-methyl-2-pyrrolidone (NMP). Thereafter, thecoatings were cured by placing the coated vials in into a preheatedfurnace at 300° C. for 30 minutes. The coated vials were thendepyrogenated (heated) at 300° C. for 12 hours.

Two vials were placed in the vial-on-vial jig depicted in FIG. 9 andabraded under a 10 N load. The abrasion procedure was repeated 4 moretimes over the same area and the coefficient of friction was determinedfor each abrasion. The vials were wiped between abrasions and thestarting point of each abrasion was positioned on a previously abradedarea and each abrasion was performed over the same “track”. The sameprocedure was repeated for loads of 30 N and 50 N. The coefficients offriction of each abrasion (i.e., A1-A5) are graphically depicted in FIG.21 for each load. As shown in FIG. 21, the coefficients of friction ofthe APS/Kapton coated vials were generally uniform and approximately0.20 or less for the abrasions introduced at loads of 10 N and 30 N.However, when the applied load was increased to 50 N, the coefficient offriction increased for each successive abrasion, with the fifth abrasionhaving a coefficient of friction slightly less than 0.40.

Example 11

Three sets of two glass vials were prepared with an APS(aminopropylsilsesquioxane) coating. Each of the vials was dip coated ina 0.1% solution of APS and heated at 100° C. in a convection oven for 15minutes. The coated vials were then depyrogenated (heated) at 300° C.for 12 hours. Two vials were placed in the vial-on-vial jig depicted inFIG. 9 and abraded under a 10 N loaded. The abrasion procedure wasrepeated 4 more times over the same area and the coefficient of frictionwas determined for each abrasion. The vials were wiped between abrasionsand the starting point of each abrasion was positioned on a previouslyabraded area and each abrasion traveled over the same “track”. The sameprocedure was repeated for loads of 30 N and 50 N. The coefficients offriction of each abrasion (i.e., A1-A5) are graphically depicted in FIG.22 for each load. As shown in FIG. 22, the coefficients of friction ofthe APS coated vials depyrogenated for 12 hours were significantlyhigher than the APS coated vials shown in FIG. 20 and were similar tocoefficients of friction exhibited by uncoated glass vials, indicatingthat the vials may have experienced a significant loss of mechanicalstrength due to the abrasions.

Example 12

Three sets of two glass vials formed from Schott Type 1B glass wereprepared with a Kapton coating. The vials were dipped into a 0.1%poly(pyromellitic dianhydride-co-4,4′-oxydianiline) amic acid solution(Kapton precursor) in N-Methyl-2-pyrrolidone (NMP). Thereafter, thecoatings were dried at 150° C. for 20 min and then cured by placing thecoated vials in into a preheated furnace at 300° C. for 30 minutes.

Two vials were placed in the vial-on-vial jig depicted in FIG. 9 andabraded under a 10 N loaded. The abrasion procedure was repeated 4 moretimes over the same area and the coefficient of friction was determinedfor each abrasion. The vials were wiped between abrasions and thestarting point of each abrasion was positioned on a previouslynon-abraded area. However, each abrasion traveled over the same “track”.The same procedure was repeated for loads of 30 N and 50 N. Thecoefficients of friction of each abrasion (i.e., A1-A5) are graphicallydepicted in FIG. 23 for each load. As shown in FIG. 23, the coefficientsof friction of the Kapton coated vials generally increased after thefirst abrasion demonstrating poor abrasion resistance of a polyimidecoating applied onto a glass without a coupling agent.

Example 13

The APS/NOVASTRAT® 800 coated vials of Example 6 were tested for theircoefficient of friction after lyophilization using a vial-on-vial jigshown in FIG. 9 with a 30 N load. No increase in coefficient of frictionwas detected after lyophilization. FIG. 24 contains Tables showing thecoefficient of friction for the APS/NOVASTRAT® 800 coated vials beforeand after lyophilization.

Example 14

The Reference Glass Composition vials were ion exchanged and coated asdescribed in Example 2. The coated vials were autoclaved using thefollowing protocol: 10 minute steam purge at 100° C., followed by a 20minute dwelling period wherein the coated glass container 100 is exposedto a 121° C. environment, followed by 30 minutes of treatment at 121° C.The coefficient of friction for autoclaved and non-autoclaved vials wasmeasured using a vial-on-vial jig shown in FIG. 9 with 30 N load. FIG.26 shows the coefficient of friction for APS/NOVASTRAT® 800 coated vialsbefore and after autoclaving. No increase in coefficient of friction wasdetected after autoclaving.

Example 15

Three sets of vials were prepared to assess the efficacy of coatings onmitigating damage to the vials. A first set of vials was coated with apolyimide outer coating later with an intermediate coupling agent layer.The outer layer consisted of the NOVASTRAT® 800 polyimide, which wasapplied as a solution of polyamic acid in dimethylacetamide and imidizedby heating to 300° C. The coupling agent layer consisted of the APS andaminophenyltrimethoxysilane (APhTMS) in a 1:8 ratio. These vials weredepyrogenated for 12 hours at 320° C. As with the first set of vials,the second set of vials was coated with a polyimide outer coating layerwith an intermediate coupling agent layer. The second set of vials wasdepyrogenated for 12 hours at 320° C. and then autoclaved for 1 hour at121° C. A third set of vials was left uncoated. Each set of vials wasthen subjected to a vial-on-vial frictive test under a 30 N load. Thecoefficient of friction for each set of vials is reported in FIG. 27.Photographs of the vial surface showing damage (or the lack of damage)experienced by each vial is also depicted in FIG. 27. As shown in FIG.27, the uncoated vials generally had a coefficient of friction greaterthan about 0.7. The uncoated vials also incurred visually perceptibledamage as a result of the testing. However, the coated vials had acoefficient of friction of less than 0.45 without any visuallyperceptible surface damage.

The coated vials were also subjected to depyrogenation, as describedabove, autoclave conditions, or both. FIG. 25 graphically depicts thefailure probability as a function of applied load in a horizontalcompression test for the vials. There was no statistical differencebetween depyrogenated vials and depyrogenated and autoclaved vials.

Example 16

Referring now to FIG. 28, vials were prepared with three differentcoating compositions to assess the effect of different ratios of silaneson the coefficient of friction of the applied coating. The first coatingcomposition included a coupling agent layer having a 1:1 ratio of GAPSto aminophenyltrimethyloxysilane and an outer coating layer whichconsisted of 1.0% NOVASTRAT® 800 polyimide. The second coatingcomposition included a coupling agent layer having a 1:0.5 ratio of GAPSto aminophenyltrimethyloxysilane and an outer coating layer whichconsisted of 1.0% Novastrat® 800 polyimide. The third coatingcomposition included a coupling agent layer having a 1:0.2 ratio of GAPSto aminophenyltrimethyloxysilane and an outer coating layer whichconsisted of 1.0% NOVASTRAT® 800 polyimide. All the vials weredepyrogenated for 12 hours at 320° C. Thereafter, the vials weresubjected to a vial-on-vial frictive test under loads of 20 N and 30 N.The average applied normal force, coefficient of friction, and maximumfrictive force (Fx) for each vial is reported in FIG. 28. As shown inFIG. 28, decreasing the amount of aromatic silane (i.e., theaminophenytrimethyloxysilane) increases the coefficient of frictionbetween the vials as well as the frictive force experienced by thevials.

Example 17

Vials formed from type 1B ion-exchanged glass were prepared withlow-friction coatings have varying ratios of silanes.

Samples were prepared with a composition which included a coupling agentlayer formed from 0.125% APS and 1.0% aminophenyltrimethyloxysilane(APhTMS), having a ratio of 1:8, and an outer coating layer formed from0.1% NOVASTRAT® 800 polyimide. The thermal stability of the appliedcoating was evaluated by determining the coefficient of friction andfrictive force of vials before and after depyrogenation. Specifically,coated vials were subjected to a vial-on-vial frictive test under a loadof 30 N. The coefficient of friction and frictive force were measuredand are plotted in FIG. 29 as a function of time. A second set of vialswere depyrogenated for 12 hours at 320° C. and subjected to the samevial-on-vial frictive test under a load of 30 N. The coefficient offriction remained the same both before and after depyrogenationindicating that the coatings were thermally stable. A photograph of thecontacted area of the glass is also shown.

Samples were prepared with a composition which included a coupling agentlayer formed from 0.0625% APS and 0.5% aminophenyltrimethyloxysilane(APhTMS), having a ratio of 1:8, and an outer coating layer formed from0.05% NOVASTRAT® 800 polyimide. The thermal stability of the appliedcoating was evaluated by determining the coefficient of friction andfrictive force of vials before and after depyrogenation. Specifically,coated vials were subjected to a vial-on-vial frictive test under a loadof 30 N. The coefficient of friction and frictive force were measuredand are plotted in FIG. 37 as a function of time. A second set of vialswere depyrogenated for 12 hours at 320° C. and subjected to the samevial-on-vial frictive test under a load of 30 N. The coefficient offriction remained the same both before and after depyrogenationindicating that the coatings were thermally stable. A photograph of thecontacted area of the glass is also shown.

FIG. 38 graphically depicts the failure probability as a function ofapplied load in a horizontal compression test for the vials withlow-friction coatings formed from 0.125% APS and 1.0%aminophenyltrimethyloxysilane (APhTMS), having a ratio of 1:8, and anouter coating layer formed from 0.1% NOVASTRAT® 800 polyimide (Shown as“260” on FIG. 38), and formed from 0.0625% APS and 0.5%aminophenyltrimethyloxysilane (APhTMS), having a ratio of 1:8, and anouter coating layer formed from 0.05% Novastrat® 800 polyimide (Shown as“280” on FIG. 38). A photograph of the contacted area of the glass isalso shown. The data shows that failure load remains unchanged fromuncoated unscratched samples for coated, depyrogenated, and scratchedsamples demonstrating glass protection from damage by the coating.

Vials were prepared with low-friction coatings have varying ratios ofsilanes. Samples were prepared with a composition which included acoupling agent layer formed from 0.5% Dynasylan® Hydrosil 1151 and 0.5%aminophenyltrimethyloxysilane (APhTMS), having a ratio of 1:1, and anouter coating layer formed from 0.05% NOVASTRAT® 800 polyimide. Thethermal stability of the applied coating was evaluated by determiningthe coefficient of friction and frictive force of vials before and afterdepyrogenation. Specifically, coated vials were subjected to avial-on-vial frictive test under a load of 30 N. The coefficient offriction and frictive force were measured and are plotted in FIG. 39 asa function of time. A second set of vials were depyrogenated for 12hours at 320° C. and subjected to the same vial-on-vial frictive testunder a load of 30 N. The coefficient of friction remained the same bothbefore and after depyrogenation indicating that the coatings werethermally stable. A photograph of the contacted area of the glass isalso shown. This suggests that hydrolysates of aminosilanes, such asaminosilsesquioxanes, are useful in the coating formulations as well.

The thermal stability of the applied coating was also evaluated for aseries of depyrogenation conditions. Specifically, type 1B ion-exchangedglass vials were prepared with a composition which included a couplingagent layer having a 1:1 ratio of GAPS (0.5%) toaminophenyltrimethyloxysilane (0.5%) and an outer coating layer whichconsisted of 0.5% NOVASTRAT® 800 polyimide. Sample vials were subjectedto one of the following depyrogenation cycles: 12 hours at 320° C.; 24hours at 320° C.; 12 hours at 360° C.; or 24 hours at 360° C. Thecoefficient of friction and frictive force were then measured using avial-on-vial frictive test and plotted as a function of time for eachdepyrogenation condition, as shown in FIG. 30. As shown in FIG. 30, thecoefficient of friction of the vials did not vary with thedepyrogenation conditions indicating that the coating was thermallystable. FIG. 40 graphically depicts the coefficient of friction aftervarying heat treatment times at 360° C. and 320° C.

Example 18

Vials were coated as described in Example 2 with a APS/NOVASTRAT 800coating. The light transmission of coated vials, as well as uncoatedvials, was measured within a range of wavelengths between 400-700 nmusing a spectrophotometer. The measurements are performed such that alight beam is directed normal to the container wall such that the beampasses through the low-friction coating twice, first when entering thecontainer and then when exiting it. FIG. 11 graphically depicts thelight transmittance data for coated and uncoated vials measured in thevisible light spectrum from 400-700 nm. Line 440 shows an uncoated glasscontainer and line 442 shows a coated glass container.

Example 19

Vials were coated with a 0.25% GAPS/0.25% APhTMS coupling agent and 1.0%NOVASTRAT® 800 polyimide and were tested for light transmission beforeand after depyrogenation at 320° C. for 12 hours. An uncoated vial wasalso tested. Results are shown in FIG. 46.

Example 20

To improve polyimide coating uniformity, the Novastrat® 800 polyamicacid was converted into polyamic acid salt and dissolved in methanol,significantly faster evaporating solvent compared to dimethylacetamide,by adding 4 g of triethylamine to 1L of methanol and then addingNOVASTRAT® 800 polyamic acid to form 0.1% solution.

Coating on 1B ion-exchanged vials formed from 1.0% GAPS/1.0% APhTMS inmethanol/water mixture and 0.1% NOVASTRAT® 800 polyamic acid salt inmethanol. The coated vials were depyrogenated for 12 h at 360° C. andundepyrogenated and depyrogenated samples were scratched in vial-on-vialjig at 10, 20 and 30 N normal loads. No glass damage was observed atnormal forces of 10 N, 20 N and 30 N. FIG. 41 shows the coefficient offriction, applied force and frictive force for the samples after a heattreatment at 360° C. for 12 hours. FIG. 42 graphically depicts thefailure probability as a function of applied load in a horizontalcompression test for the samples. Statistically the sample series at 10N, 20N, and 30 N were indistinguishable from each other. The low loadfailure samples broke from origins located away from the scratch.

The thickness of the coating layers was estimated using ellipsometry andscanning electron microscopy (SEM), shown in FIGS. 43-45, respectively.The samples for coating thickness measurements were produced usingsilicon wafer (ellipsometry) and glass slides (SEM). The methods showthicknesses varying from 55 to 180 nm for silsesquioxane tie-layer and35 nm for NOVASTRAT® 800 polyamic acid salt.

Example 21

Plasma cleaned Si wafer pieces were dip coated using 0.5% GAPS, 0.5%APhTMS solution in 75/25 methanol/water vol/vol mixture. The coating wasexposed to 120° C. for 15 minutes. The coating thickness was determinedusing ellipsometry. Three samples were prepared, and had thicknesses of92.1 nm, 151.7 nm, and 110.2 nm, respectively, with a standard deviationof 30.6 nm.

Glass slides were dip coated and examined with a scanning electronmicroscope. FIG. 43 shows an SEM image glass slide dipped in a coatingsolution of 1.0% GAPS, 1.0% APhTMS, and 0.3% NMP with an 8 mm/s pull outrate after a curing at 150° C. for 15 minutes. The coating appears to beabout 93 nm thick. FIG. 44 shows an SEM image glass slide dipped in acoating solution of 1.0% GAPS, 1.0% APhTMS, and 0.3% NMP with a 4 mm/spull out rate after a curing at 150° C. for 15 minutes. The coatingappears to be about 55 nm thick. FIG. 45 shows an SEM image glass slidedipped in a coating solution of 0.5 NOVASTRAT® 800 solution with a 2mm/s pull up rate after a curing at 150° C. for 15 min and heattreatment at 320° C. for 30 minutes. The coating appears to be about 35nm thick.

Comparative Example A

Glass vials formed from a Type 1B glass were coated with a dilutedcoating of Bayer Silicone aqueous emulsion of Baysilone M with a solidscontent of about 1-2%. The vials were treated at 150° C. for 2 hours todrive away water from the surface leaving a polydimethylsiloxane coatingon the exterior surface of the glass. The nominal thickness of thecoating was about 200 nm. A first set of vials were maintained inuntreated condition (i.e., the “as-coated vials”). A second set of vialswere treated at 280° C. for 30 minutes (i.e., the “treated vials”). Someof the vials from each set were first mechanically tested by applying ascratch with a linearly increasing load from 0-48 N and a length ofapproximately 20 mm using a UMT-2 tribometer. The scratches wereevaluated for coefficient of friction and morphology to determine if thescratching procedure damaged the glass or if the coating protected theglass from damage due to scratching.

FIG. 33 is a plot showing the coefficient of friction, scratchpenetration, applied normal force, and frictional force (y-ordinates) asa function of the length of the applied scratch (x-ordinate) for theas-coated vials. As graphically depicted in FIG. 33, the as-coated vialsexhibited a coefficient of friction of approximately 0.03 up to loads ofabout 30 N. The data shows that below approximately 30 N, the COF isalways below 0.1. However, at normal forces greater than 30 N, thecoating began to fail, as indicated by the presence of glass checkingalong the length of scratch. Glass checking is indicative of glasssurface damage and an increased propensity of the glass to fail as aresult of the damage.

FIG. 34 is a plot showing the coefficient of friction, scratchpenetration, applied normal force, and frictional force (y-ordinates) asa function of the length of the applied scratch (x-ordinate) for thetreated vials. For the treated vials, the coefficient of frictionremained low until the applied load reached a value of approximately 5N. At that point the coating began to fail and the glass surface wasseverely damaged as evident from the increased amount of glass checkingwhich occurred with increasing load. The coefficient of friction of thetreated vials increased to about 0.5. However, the coating failed toprotect the surface of the glass at loads of 30 N following thermalexposure, indicating that the coating was not thermally stable.

The vials were then tested by applying 30 N static loads across theentire length of the 20 mm scratch. Ten samples of as-coated vials andten samples of treated vials were tested in horizontal compression byapplying a 30 N static load across the entire length of the 20 mmscratch. None of the as-coated samples failed at the scratch while 6 ofthe 10 treated vials failed at the scratch indicating that the treatedvials had lower retained strength.

Comparative Example B

A solution of Wacker Silres MP50 (part #60078465 lot #EB21192) wasdiluted to 2% and was applied to vials formed from the Reference GlassComposition. The vials were first cleaned by applying plasma for 10seconds prior to coating. The vials were dried at 315° C. for 15 minutesto drive off water from the coating. A first set of vials was maintainedin “as-coated” condition. A second set of vials was treated for 30minutes at temperatures ranging from 250° C. to 320° C. (i.e., “treatedvials”). Some of the vials from each set were first mechanically testedby applying a scratch with a linearly increasing load from 0-48N and alength of approximately 20 mm using a UMT-2 tribometer. The scratcheswere evaluated for coefficient of friction and morphology to determineif the scratching procedure damaged the glass or if the coatingprotected the glass from damage due to scratching.

FIG. 35 is a plot showing the coefficient of friction, scratchpenetration, applied normal force, and frictional force (y-ordinates) asa function of the length of the applied scratch (x-ordinate) for theas-coated vials. The as-coated vials exhibited damage to the coating,but no damage to the glass.

FIG. 36 is a plot showing the coefficient of friction, scratchpenetration, applied normal force, and frictional force (y-ordinates) asa function of the length of the applied scratch (x-ordinate) for thetreated vials treated at 280° C. The treated vials exhibited significantglass surface damage at applied loads greater than about 20 N. It wasalso determined that the load threshold to glass damage decreased withincreasing thermal exposure temperatures, indicating that the coatingsdegraded with increasing temperature (i.e., the coating is not thermallystable). Samples treated at temperatures lower than 280° C. showed glassdamage at loads above 30N.

Comparative Example C

Vials formed from the Reference Glass Composition were treated withEvonik Silikophen P 40/W diluted to 2% solids in water. The samples werethen dried at 150° C. for 15 minutes and subsequently cured at 315° C.for 15 minutes. A first set of vials was maintained in “as-coated”condition. A second set of vials was treated for 30 minutes at atemperature of 260° C. (i.e., “the 260° C. treated vials”). A third setof vials was treated for 30 minutes at a temperature of 280° C. (i.e.,“the 280° C. treated vials”). The vials were scratched with a staticload of 30 N using the testing jig depicted in FIG. 9. The vials werethen tested in horizontal compression. The 260° C. treated vials and the280° C. treated vials failed in compression while 2 of 16 of theas-coated vials failed at the scratch. This indicates that the coatingdegraded upon exposure to elevated temperatures and, as a result, thecoating did not adequately protect the surface from the 30 N load.

Example 22

Pharmaceutical Filling Line Trial 1

Within an isolator room, a filling line trial for approximately 8,000conventional uncoated type 1B glass 3 mL vials (hereinafter “comparativeuncoated vial samples”) and approximately 8,000 coated 3 mL glass vialshaving the composition and coating from Example 1 above (“coated glassvial samples”) was conducted. The filling line is a conventionalisolator style filling line that fills up to 350 vials/min. Thedepyrogenation temperature is greater than 300° C. The estimated time onthe line for each vial was about 30-40 minutes. The comparative uncoatedvial samples and the coated glass vial samples were both filled with1.25 mL of water. The line was cleaned using typical methods in betweentrials. For the conventional vials, Schott Fiolax 3 mL vials were used.

During this trial, there was an explicit focus to assess the particulategeneration performance. Airborne and surface particles in the isolatorand in-solution particles were all monitored. Supplemental airbornemonitoring in the isolator was completed using four-inch silicon wafersthat were placed at various locations. Surface particle monitoring wascompleted by wiping surfaces with adhesive carbon tape and performingSEM analysis prior to and following each trial. Manipulation of particlemonitoring wafers and carbon tape were performed without opening theisolator. Particles in the liquid drug product were assessed by lightobscuration according to USP <788> with samples from the beginning,middle and end of the trial. The isolator portion of the line wascleaned using standard protocols prior to the trial of each vial type.

Optical inspection revealed that both frictive surface damage andsub-surface fractures (glass checks) can be observed on thesecomparative uncoated vial samples (See FIG. 47) after the processingline trial, as will be explained. As shown in FIG. 47, the vial iscovered with small checks, scratches and a ‘wear ring’ is present on thebarrel near the shoulder indicating numerous impacts with adjacent glassvials during processing. The frictive surface damage results inparticles of less than 50 μm to be generated. As shown in FIG. 47,evidence of large ‘holes’ in the surface suggest large particles ofglass could also be ejected from the surface. Without being limited toany particular theory, larger particles are more likely to be createdfrom a two-step process. In the first step, a glass check is formed froman initial impact, thereby creating a surface fracture when the surfaceis in tensile force. The second step occurs when the same damagelocation experiences another impact or frictive contact which therebyejects the larger particle. Evidence of particles greater than 120 μmbeing ejected from uncoated vials was found on 8% of vials inspected. Incontrast, FIG. 48 illustrates images of the coated glass vial samplesthat were processed similarly, yet only manifested what was determinedto be minor coating scuffing. No glass damage was observed.

In addition to characterizing the improvements qualitatively, twomethods were utilized to assess and quantify particle contaminationduring the actual trial. Specifically, surfaces within the isolator werewiped with adhesive carbon tape to inspect for surface particlecontamination. Silicon wafers were also used as airborne getteringplates. The wafers were 4″ in diameter and placed in the isolator nearthe accumulator table at the same elevation as the vial mouth.Additionally, four silicon wafers were in the isolator and four siliconwafers were placed outside the isolator at the depyrogenation tunnelentrance and near the washing area.

The carbon tape was analyzed by scanning electron microscopy (SEM) forparticle density and size analysis. For the uncoated vial samples, theparticle composition was analyzed by energy dispersive x-rayspectroscopy (EDX) to determine if the particle is glass. Between 4 and43% of particles analyzed were from borosilicate glass. EDX was alsoused to distinguish between particles from the comparative uncoated vialsamples and particles from the coated vial samples. FIGS. 49A and 49Billustrate the difference in EDX spectra between the two compositions.Referring to FIG. 49B, which is the EDX spectra of the uncoatedborosilicate vial sample, the presence of potassium and magnesiumindicated the presence of glass particles on the carbon tape. Incontrast as shown in FIG. 49A, the EDX spectra of the present coatedvial samples indicates that none of the particles on the carbon tapewere the glass composition of the coated vial samples.

Despite the standard isolator cleaning protocol, carbon tape indicatedthe presence of a substantial quantity of conventional glass particlesprior to the line trial with the coated glass vial. This was alsoconfirmed by compositional analysis. Without being bound by theory, somequantity of sub-visible particles detected during the coated vial trialis a result of the residual particle contamination left on the lineafter the control trial run with conventional vials. With this result inmind, even greater particle reduction would be achieved if theunderlying conventional glass particle contamination was fully removed.FIG. 56 illustrates representative SEM images from the accumulator tablefollowing the trial. As shown, a significant quantity of glass particleswere observed ranging in size from 1 to 15 μm.

Alternatively, clean silicon wafers of 100 mm size were placed invarious regions near the processed containers in order to captureairborne particles during the trial. Wafers were placed at bothcontainer mouth elevation and near exhaust ports. A total of 156particles were collected with 4 wafers in the isolator. Compared to thecontrol run with conventional glass vials, the trial with the coatedglass vial showed an 85% reduction in airborne particles in size from 20to 120 μm near the accumulator table as indicated by the settlingplates. The wafers were optically inspected and the nature of theparticles was characterized.

Based on sampling, approximately half of the particles identified wereobvious glass particles with a size range of 20 to 120 μm. Usingqualitative visual inspection, the remainder of the particles wereeither fibrous or were unable to be determined. Over half of theparticles were collected at the same elevation as the container mouth.It is worth noting that no container break events occurred in theisolator during this trial, thereby demonstrating that glass particlesare still being generated despite a lack of broken containers.

The light obscuration technique according to USP <788> was used tomeasure particles in solution within vials filled during the trial.Particle reduction in the isolator environment correlates to particlereduction in containers (e.g., vials). Referring to Table 2 below, theanalysis indicated at least a 50% reduction in average glass particlecount for generated glass particles from coated containers compared toan average particle count of generated glass particles from uncoatedglass containers. The average glass particle count was computed forglass particles equal to or greater than 10 μm and glass particles equalto or greater than 25 μm using light obscuration according to UnitedStates Pharmacopoeia Standard 788. The % reduction was determined forthe sum of the average glass particle count for glass particles equal toor greater than 10 μm and the average glass particle count for glassparticles equal to or greater than 25 μm.

TABLE 2 Glass Filling line trial 2-10 μm >10 μm >25 μm USP limit None6000 600 Coated Glass Beginning 685.9 11.5 0.4 Vial Sample Coated GlassMiddle 678.1 11.7 0.3 Vial Sample Coated Glass End 918.6 16.1 0.0 VialSample Coated Glass 760.9 13.1 0.24 Vial Sample (Average) ComparativeBeginning 1261.7 19.7 0.1 Uncoated Glass Vial Sample Comparative Middle1393.4 31.4 1.2 Uncoated Glass Vial Sample Comparative End 1296.3 31.60.0 Uncoated Glass Vial Sample Comparative 1317.2 27.6 0.42 UncoatedGlass Vial Sample (Average)

The above data confirms that glass-to-glass vial contact is asignificant source of particles. It also suggests that environmentalcontrols such as vertical laminar flow are not completely effective atpreventing particles generated on the line from entering the vial. Evenin well-designed isolator systems, horizontal surfaces of the equipment(e.g. conveyor surfaces) and even the bottom of the vial disruptvertical laminar flow that is intended to sweep away contaminants.

The particle reduction results for this trial are summarized in Table 3.

TABLE 3 Control Coated Vial % reduction Airborne particle count (wafer156 23 85% settling plate) Solution particle counts (2-10 μm)* 1318 76142% Solution particle counts (>10 μm)* 28 14 50% Solution particlecounts (>25 μm)* 0.42 0.23 45% *Measured using an average of 40 samplesfrom beginning, middle and end of trial

Example 23

Laboratory Simulations—Scratch Test

Laboratory simulations were also used to replicate the interactions ofthe vials on pharmaceutical filling lines. Two types of simulations wereevaluated in order to separate the effects of static loading and impactevents. A vial scratching test was used to evaluate effect of staticloading. Referring to the schematic of the test setup of FIG. 50, twocontainers are oriented orthogonally in a fixture with contact betweenbarrels. A Nanovea CB500 mechanical tester applies a controlled,constant load and translates one of the vials linearly. As shown, thetranslation direction is 45 degrees relative to the barrel direction inorder to produce a scratch in virgin surfaces on each container. Movingload forces are applied in order to create controlled scratch along thebarrel. The test setup results in the scratches being produced in avirgin surface on both parts as the vials are moved. The load iscontrolled using a feedback loop. During the scratch generation,particles are ejected and are monitored in a nearby particle debrisfield. The debris field is microscopically inspected and the particlescan be automatically counted using ImageJ vision software.

The comparative uncoated glass vial samples and the coated glass vialsamples were tested under the vial scratch test with an applied loadranging between 1 to 30 N representing the range of forces measured onan actual filling line. The subsequent damage on the pair of vials wasinspected using optical microscopy. The size of the damage site and thedebris field increased in size with larger loads as result of increasedHertzian contact area. Furthermore, when a larger load was applied,particles were ejected further away resulting in a larger debris field.Fractographic analysis revealed that the morphology, size and severityof damage compares well with damage observed on vials processed througha filling line.

High resolution optical images of the debris fields were captured andanalyzed by software to determine particle distributions. Depending onthe load, hundreds to thousands of glass particles were generated from asingle 1 mm scratch of the uncoated borosilicate glass vial samples assummarized in FIG. 51. All of the particles observed were in thesub-visible range (<50 μm) with the majority of particles being lessthan 5 μm. As shown, the particle distribution at each size range issimilar regardless of load between 1 and 30 N.

Referring to FIG. 52, the effect of translational scratch speed on theuncoated borosilicate glass vial samples was also examined over therange of 6 to 120 mm/min to simulate the observed wide range of thespeed of interactions observed on a filling line. A comparison of thedistributions versus speed is shown in FIG. 52 for a 30 N applied load.Thus, the particle size distribution for each size range is independentover the range of applied loads and speeds evaluated using this method,thereby demonstrating that the mechanism of particle generation isconsistent over the range of static interactions on the filling line.

In order to assess the efficiency of particle collection by the opticalinspection of the debris field, damage sites were also imaged byscanning electron microscopy. The morphology of the scratch damage didnot vary significantly by load over the range studied. The imagesindicated that the damage site contained a significant number ofparticles that were not ejected to the debris field; however, the sizerange of the particles was consistent with those counted in the debrisfield. Therefore, the debris field particles represent only a portion ofthe total particles generated. Even with the conservative view thatexcludes particles which are not ejected to the debris field, this studyshows that a single glass to glass contact event can generate thousandsof particles while the container is being processed in the filling linewhere it is open and vulnerable to particle contamination. Thus, theparticle distribution generated is independent of the nature of thefrictive contact event over the range of loads and speeds tested.

An SEM image of the debris field is illustrated in FIG. 53 confirmingthe particle sizes as measured optically. The morphology of theparticles is jagged and irregular consistent with those particlesidentified in the damage site. Gentle manipulation of the scratchedsamples revealed that the particles are not well adhered to the glasssurface. Lightly blown air or physical contact by a swab easily removedthe particles from both the debris field and from the damaged area. Asfurther evidence that particles are not well adhered to the glasssurface, parts processed through a filling line lack an associateddebris field near damaged areas. With the aid of air flow and physicalcontact in the filling area, it is anticipated that the majority of theparticles are introduced into the filling line environment when thedamage is originally created.

Similar scratch test results for coating coated glass vial samples didnot produce any detectable glass particles. Although some coatingscuffing is noted, well defined or systematically generated coatingparticles were also not observed. Thus the scratch test resultsdemonstrated the same particle reduction benefit as demonstrated in thefilling line trial.

Example 24

Pharmaceutical Filling Line Trial 2

An additional trial was undertaken to quantify the particle reductionbenefit in the filling line environment. This trial included processinggreater than 1 million 3 mL Schott IB vials on a conventional high-speedbarrier-style filling line with downward laminar flow. The typical vialfilling speed is 400-550 vials/min. The protocol was specificallyfocused on assessing particle response. In-line monitoring of airborneparticles in the barrier was performed using conventional monitors usedfor monitoring filling lines (sensitive to particle sizes of 0.5 μm orgreater). In addition, a detailed record for each operator interventionwas also maintained. The results were then compared to a conventionalglass vial run. A standard line cleaning was performed prior to eachrun.

While processing conventional glass vials on the fill line, frequentoperator interventions as noted in Table 4 below were required toalleviate jammed, tipped or broken vials or to clean specific containerguide surfaces. Interventions tend to further elevate the contaminationrisk of all airborne particles by disrupting the laminar flow anddisturbing settled particles. Referring to Table 4 below, with thecoated glass vial, the machinability improved remarkably versus thecontrol as evidenced by a 61% reduction in interventions and a 36%increase in effective line throughput. This suggests an overall lowerlevel of contamination than what is traditionally experienced during afilling campaign. Particle monitoring showed a 96% reduction in peakparticle levels above the post-depyrogenation accumulator table, wherethe vials are open and at risk to environmental contamination.Additionally, there was a decrease in particle spikes, which aretemporary increases in airborne particle counts due to the disturbanceof air flow, the dislodging of settled particles, or another temporarycause. Particle spikes are measured by determining the number ofparticles over time and locating time intervals wherein there is a sharpincrease or decrease of particle generation. Complete line trial resultsare summarized in Table 4.

TABLE 4 Control Coated Glass Vial Peak particle count (0.5 μm/CM) 8609337 Total particle spikes 59 36 Particle spikes at in-feed 50 4Interventions 247 95

Example 25

Comparison to Silicone Coated Borosilicate Cartridges

Referring to FIGS. 54 and 55, the scratch test performance of thepresent coated ion exchanged glass cartridges having the composition ofExample 1 and the Schott FIOLAX® silicone coated borosilicate cartridges(Comparative Example A) is shown, respectively. Comparing FIG. 54, whichis the Weibull plot of Example 1, to FIG. 55, which is the Weibull plotof Comparative Example A, it is readily apparent that the Example 1cartridge demonstrates approximately a tenfold improvement in failureload. As used herein, “failure load” is the load at which the glassarticle breaks.

For Example 1, the Weibull plot of FIG. 54 shows that there is nostatistically significant difference in the article performance (asdemonstrated by failure load) whether the scratch is conducted at a 1 Nload or a 30 N load. Said another way, the Example 1 cartridge showsgood wear resistance whether a 1 N load or 30 N load is used. Incontrast, the Comparative Example A silicone coated article depicted inFIG. 55 shows a substantial change in failure load due to increasingscratch loads of 1 to 30 N. This deviation in FIG. 55 shows that thesilicone is not fully protecting the vial because of coatingdeterioration. The coating deterioration results in glass damage andparticle generation for the vials of Comparative Example A.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to the embodiments describedherein without departing from the spirit and scope of the claimedsubject matter. Thus it is intended that the specification cover themodifications and variations of the various embodiments described hereinprovided such modification and variations come within the scope of theappended claims and their equivalents.

What is claimed is:
 1. A coated glass article comprising: a glass bodyformed from an alkali aluminosilicate glass having a Class HGA 1hydrolytic resistance when tested according to the ISO 720-1985 testingstandard and having a first surface and a second surface opposite thefirst surface, wherein the first surface is an exterior surface of theglass body; and a coating disposed on at least a portion of the exteriorsurface of the glass body, the coating comprising a polymer and acoupling agent layer, wherein the polymer comprises a polyimide, thecoupling agent layer comprises a silsesquioxane, and the coated glassarticle reduces glass particle generation when the coated glass articleundergoes processing, wherein the coated glass article demonstrates atleast a 50% reduction in average glass particle count for generatedglass particles compared to an average particle count of generated glassparticles by an uncoated glass article that undergoes the processing,wherein the average glass particle count is computed for glass particlesequal to or greater than 10 μm and glass particles equal to or greaterthan 25 μm using light obscuration according to United StatesPharmacopoeia Standard 788 and the % reduction is determined for the sumof the average glass particle count for glass particles equal to orgreater than 10 μm and the average glass particle count for glassparticles equal to or greater than 25 μm.
 2. The coated glass article ofclaim 1 wherein the processing of the coated glass article involvessubjecting the coated glass article or the coated glass article tonon-breakage inducing glass contact in pharmaceutical glass fillinglines.
 3. The coated glass article of claim 2 wherein the non-breakageinducing glass contact involves glass to glass contact.
 4. The coatedglass article of claim 1 wherein the coated glass article demonstrates areduction in average glass particle count of at least 75% compared tothe average glass particle count for the uncoated glass article.
 5. Thecoated glass article of claim 4 wherein the coated glass articledemonstrates a reduction in average glass particle count of at least 90%compared to the average glass particle count for the uncoated glassarticle.
 6. The coated glass article of claim 5 wherein the coated glassarticle demonstrates a reduction in average glass particle count of atleast 99% compared to the average glass particle count for the uncoatedglass article.
 7. The coated glass article of claim 1 wherein the firstsurface comprises side walls of a container, a bottom of the container,or both.
 8. The coated glass article of claim 1 wherein the firstsurface is only partially coated with the coating.
 9. The coated glassarticle of claim 1 wherein the processing involves thermal treatmentsteps.
 10. The coated glass article of claim 9 wherein the thermaltreatment steps include one or more of depyrogenation, autoclaving, orlyophilization.
 11. The coated glass article of claim 1, wherein thecoated glass article is a coated glass vial.
 12. The coated glassarticle of claim 2 wherein the average glass particle count for glassparticles with a size of 25 to 50 μm is from 0.01 to 1 when the coatedglass article has a container volume of 3 mL and undergoes filling; andwherein the average glass particle count for glass particles with a sizeof 10 to 25 μm is from 1 to 20 when the coated glass article has acontainer volume of 3 mL and undergoes filling.
 13. The coated glassarticle of claim 2 wherein the pharmaceutical glass filling lineinvolves subjecting the coated glass article to horizontal compressionforces ranging from 0.1 N to 30 N at scratch velocities ranging from 6to 120 mm/min.
 14. The coated glass article of claim 1 wherein thecoated glass article is chemically strengthened glass.
 15. A coatedglass article comprising: a glass body formed from an alkalialuminosilicate glass having a Class HGA 1 hydrolytic resistance whentested according to the ISO 720-1985 testing standard and having a firstsurface and a second surface opposite the first surface, wherein thefirst surface is an exterior surface of the glass body; and a coatingdisposed on at least a portion of the exterior surface of the glassbody, the coating comprising a polymer and a coupling agent layer,wherein: the polymer comprises a polyimide; the coupling agent layercomprises a silsesquioxane; and the coated glass article reduces glassparticle formation caused by non-breakage inducing glass contact inpharmaceutical glass filling lines, the reduction in glass particleformation being defined as follows: wherein an average glass particlecount of glass particles having a size of equal to or greater than 10 μmand equal to or greater than 25 μm is below allowable levels defined byUnited States Pharmacopoeia Reference Standard 788, the average particlecount being computed using light obscuration; and wherein the coatedglass article demonstrates at least a 50% reduction in average glassparticle count for generated glass particles compared to an averageglass particle count of generated glass particles by an uncoated glassarticle in the pharmaceutical glass filling lines, wherein the averageglass particle count is computed for glass particles equal to or greaterthan 10 μm and glass particles equal to or greater than 25 μm usinglight obscuration according to United States Pharmacopoeia Standard 788and the % reduction is determined for the sum of the average glassparticle count for glass particles equal to or greater than 10 μm andthe average glass particle count for glass particles equal to or greaterthan 25 μm.
 16. The coated glass article of claim 15 wherein the coatedglass article demonstrates a reduction in average glass particle countof at least 75% compared to the average glass particle count for theuncoated glass article.
 17. The coated glass article of claim 16 whereinthe coated glass article demonstrates a reduction in average glassparticle count of at least 90% compared to the average glass particlecount for the uncoated glass article.
 18. The coated glass article ofclaim 17 wherein the coated glass article demonstrates a reduction inaverage glass particle count of at least 99% compared to the averageglass particle count for the uncoated glass article.
 19. The coatedglass article of claim 15, wherein the coated glass article is a coatedglass vial.
 20. The coated glass article of claim 15, wherein theaverage glass particle count for glass particles with a size of 25 to 50μm is from 0.01 to 1 when the coated glass article has a containervolume of 3 mL and undergoes filling; and wherein the average glassparticle count for glass particles with a size of 10 to 25 μm is from 1to 20 when the coated glass article has a container volume of 3 mL andundergoes filling.
 21. The coated glass article of claim 15, wherein thepharmaceutical glass filling line involves subjecting the coated glassarticle to horizontal compression forces ranging from 0.1 N to 30 N atscratch velocities ranging from 6 to 120 mm/min.
 22. The coated glassarticle of claim 15 wherein the coated glass article is chemicallystrengthened glass.
 23. A coated glass article comprising: a glass bodyformed from a borosilicate glass that meets the Type 1 criteriaaccording to USP <660> and having a first surface and a second surfaceopposite the first surface, wherein the first surface is an exteriorsurface of the glass body; and a coating disposed on at least a portionof the exterior surface of the glass body, the coating comprising apolymer and a coupling agent layer, wherein the polymer comprises apolyimide, the coupling agent layer comprises a silsesquioxane, and thecoated glass article reduces particle generation when the coated glassarticle undergoes processing, wherein the coated glass articledemonstrates at least a 50% reduction in average glass particle countfor generated glass particles compared to an average glass particlecount of generated sub-visible glass particles by an uncoated glassarticle that undergoes the processing, wherein the average glassparticle count is computed for glass particles equal to or greater than10 μm and glass particles equal to or greater than 25 μm using lightobscuration according to United States Pharmacopoeia Standard 788 andthe % reduction is determined for the sum of the average glass particlecount for glass particles equal to or greater than 10 μm and the averageglass particle count for glass particles equal to or greater than 25 μm.24. The coated glass article of claim 23 wherein the processing of thecoated glass article involves subjecting the coated glass article or thecoated glass article to non-breakage inducing glass contact inpharmaceutical glass filling lines.
 25. The coated glass article ofclaim 24 wherein the non-breakage inducing glass contact involves glassto glass contact.
 26. The coated glass article of claim 23 wherein thecoated glass article demonstrates a reduction in average glass particlecount of at least 75% compared to the average glass particle count forthe uncoated glass article.
 27. The coated glass article of claim 26wherein the coated glass article demonstrates a reduction in averageglass particle count of at least 90% compared to the average glassparticle count for the uncoated glass article.
 28. The coated glassarticle of claim 27 wherein the coated glass article demonstrates areduction in average glass particle count of at least 99% compared tothe average glass particle count for the uncoated glass article.
 29. Thecoated glass article of claim 23 wherein the first surface comprisesside walls of a container, a bottom of the container, or both.
 30. Thecoated glass article of claim 23 wherein the first surface is onlypartially coated with the coating.
 31. The coated glass article of claim23 wherein the processing involves thermal treatment steps.
 32. Thecoated glass article of claim 31 wherein the thermal treatment stepsinclude one or more of depyrogenation, autoclaving, or lyophilization.33. The coated glass article of claim 23, wherein the coated glassarticle is a coated glass vial.
 34. The coated glass article of claim 24wherein the average glass particle count for glass particles with a sizeof 25 to 50 μm is from 0.01 to 1 when the coated glass article has acontainer volume of 3 mL and undergoes filling; and wherein the averageglass particle count for glass particles with a size of 10 to 25 μm isfrom 1 to 20 when the coated glass article has a container volume of 3mL and undergoes filling.
 35. The coated glass article of claim 24wherein the pharmaceutical glass filling line involves subjecting thecoated glass article to horizontal compression forces ranging from 0.1 Nto 30 N at scratch velocities ranging from 6 to 120 mm/min.
 36. Thecoated glass article of claim 23 wherein the coated glass article ischemically strengthened glass.
 37. A coated glass article comprising: aglass body formed from a borosilicate glass that meets the Type 1criteria according to USP <660> and having a first surface and a secondsurface opposite the first surface, wherein the first surface is anexterior surface of the glass body; and a coating disposed on at least aportion of the exterior surface of the glass body, the coatingcomprising a polymer and a coupling agent layer, wherein: the polymercomprises a polyimide; the coupling agent layer comprises asilsesquioxane; and the coated glass article reduces glass particleformation caused by non-breakage inducing glass contact inpharmaceutical glass filling lines, the reduction in glass particleformation being defined as follows: wherein an average glass particlecount of glass particles having a size of equal to or greater than 10 μmand equal to or greater than 25 μm is below allowable levels defined byUnited States Pharmacopoeia Reference Standard 788, the average particlecount being computed using light obscuration; and wherein the coatedglass article demonstrates at least a 50% reduction in average glassparticle count for generated glass particles compared to an averageglass particle count of generated glass particles by an uncoated glassarticle in the pharmaceutical glass filling lines, wherein the averageglass particle count is computed for glass particles equal to or greaterthan 10 μm and glass particles equal to or greater than 25 μm usinglight obscuration according to United States Pharmacopoeia Standard 788and the % reduction is determined for the sum of the average glassparticle count for glass particles equal to or greater than 10 μm andthe average glass particle count for glass particles equal to or greaterthan 25 μm.
 38. The coated glass article of claim 37 wherein the coatedglass article demonstrates a reduction in average glass particle countof at least 75% compared to the average glass particle count for theuncoated glass article.
 39. The coated glass article of claim 37 whereinthe coated glass article demonstrates a reduction in average glassparticle count of at least 90% compared to the average glass particlecount for the uncoated glass article.
 40. The coated glass article ofclaim 39 wherein the coated glass article demonstrates a reduction inaverage glass particle count of at least 99% compared to the averageglass particle count for the uncoated glass article.
 41. The coatedglass article of claim 37, wherein the coated glass article is a coatedglass vial.
 42. The coated glass article of claim 37, wherein theaverage glass particle count for glass particles with a size of 25 to 50μm is from 0.01 to 1 when the coated glass article has a containervolume of 3 mL and undergoes filling; and wherein the average glassparticle count for glass particles with a size of 10 to 25 μm is from 1to 20 when the coated glass article has a container volume of 3 mL andundergoes filling.
 43. The coated glass article of claim 37, wherein thepharmaceutical glass filling line involves subjecting the coated glassarticle to horizontal compression forces ranging from 0.1 N to 30 N atscratch velocities ranging from 6 to 120 mm/min.
 44. The coated glassarticle of claim 37 wherein the coated glass article is chemicallystrengthened glass.